rs7051368

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_194277.3(FRMD7):c.1101T>C(p.Asn367Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 1,205,850 control chromosomes in the GnomAD database, including 3,561 homozygotes. There are 33,772 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 318 hom., 2541 hem., cov: 22)

Exomes 𝑓: 0.089 ( 3243 hom. 31231 hem. )

Consequence

FRMD7
NM_194277.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.160

Publications

2 publications found

Variant links:

Genes affected

FRMD7 (HGNC:8079): (FERM domain containing 7) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of neuron projection development. Predicted to act upstream of or within several processes, including negative regulation of stress fiber assembly; positive regulation of lamellipodium assembly; and positive regulation of small GTPase mediated signal transduction. Located in cytosol; nucleoplasm; and plasma membrane. Implicated in congenital nystagmus 1. [provided by Alliance of Genome Resources, Apr 2022]

FRMD7 Gene-Disease associations (from GenCC):

nystagmus 1, congenital, X-linked
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

FRMD7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant X-132078916-A-G is Benign according to our data. Variant chrX-132078916-A-G is described in ClinVar as Benign. ClinVar VariationId is 263086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD7	NM_194277.3 link	c.1101T>C	p.Asn367Asn	synonymous_variant	Exon 12 of 12	ENST00000298542.9	NP_919253.1	Q6ZUT3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FRMD7	ENST00000298542.9 link	c.1101T>C	p.Asn367Asn	synonymous_variant	Exon 12 of 12	1	NM_194277.3	ENSP00000298542.3	Q6ZUT3-1
FRMD7	ENST00000464296.1 link	c.1056T>C	p.Asn352Asn	synonymous_variant	Exon 12 of 12	1		ENSP00000417996.1	Q6ZUT3-2
FRMD7	ENST00000370879.5 link	c.741T>C	p.Asn247Asn	synonymous_variant	Exon 8 of 8	1		ENSP00000359916.1	X6R7S7

Frequencies

GnomAD3 genomes

AF:

0.0856

AC:

9517

AN:

111142

Hom.:

317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0916

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0599

Gnomad ASJ

AF:

0.0523

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0150

Gnomad FIN

AF:

0.0906

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.0982

Gnomad OTH

AF:

0.0927

GnomAD2 exomes

AF:

0.0688

AC:

12461

AN:

181051

AF XY:

0.0666

show subpopulations

Gnomad AFR exome

AF:

0.0938

Gnomad AMR exome

AF:

0.0372

Gnomad ASJ exome

AF:

0.0494

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0836

Gnomad NFE exome

AF:

0.0985

Gnomad OTH exome

AF:

0.0781

GnomAD4 exome

AF:

0.0892

AC:

97648

AN:

1094652

Hom.:

3243

Cov.:

AF XY:

0.0867

AC XY:

31231

AN XY:

360286

show subpopulations

African (AFR)

AF:

0.0980

AC:

2581

AN:

26339

American (AMR)

AF:

0.0399

AC:

1404

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.0519

AC:

1005

AN:

19367

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30188

South Asian (SAS)

AF:

0.0163

AC:

882

AN:

54060

European-Finnish (FIN)

AF:

0.0841

AC:

3405

AN:

40493

Middle Eastern (MID)

AF:

0.111

AC:

457

AN:

4119

European-Non Finnish (NFE)

AF:

0.100

AC:

84073

AN:

838902

Other (OTH)

AF:

0.0835

AC:

3840

AN:

45980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

3208

6416

9624

12832

16040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3080

6160

9240

12320

15400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0857

AC:

9527

AN:

111198

Hom.:

318

Cov.:

AF XY:

0.0760

AC XY:

2541

AN XY:

33432

show subpopulations

African (AFR)

AF:

0.0918

AC:

2809

AN:

30597

American (AMR)

AF:

0.0598

AC:

625

AN:

10448

Ashkenazi Jewish (ASJ)

AF:

0.0523

AC:

138

AN:

2641

East Asian (EAS)

AF:

0.00

AC:

AN:

3514

South Asian (SAS)

AF:

0.0143

AC:

AN:

2657

European-Finnish (FIN)

AF:

0.0906

AC:

537

AN:

5929

Middle Eastern (MID)

AF:

0.107

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.0982

AC:

5203

AN:

52999

Other (OTH)

AF:

0.0916

AC:

139

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

319

638

956

1275

1594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0912

Hom.:

4553

Bravo

AF:

0.0845

EpiCase

AF:

0.0990

EpiControl

AF:

0.0990

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nystagmus 1, congenital, X-linked

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.68

(source)

DANN

Benign

0.63

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over