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.1533T>C(p.Ile511Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,207,818 control chromosomes in the GnomAD database, including 37,254 homozygotes. There are 114,136 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 4446 hom., 9557 hem., cov: 22)

Exomes 𝑓: 0.29 ( 32808 hom. 104579 hem. )

Consequence

FRMD7
NM_194277.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.390

Publications

16 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=-0.94).

BP6

Variant X-132078484-A-G is Benign according to our data. Variant chrX-132078484-A-G is described in ClinVar as Benign. ClinVar VariationId is 263088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194277.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD7	NM_194277.3	MANE Select	c.1533T>C	p.Ile511Ile	synonymous	Exon 12 of 12	NP_919253.1
	FRMD7	NM_001306193.2		c.1488T>C	p.Ile496Ile	synonymous	Exon 12 of 12	NP_001293122.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FRMD7	ENST00000298542.9	TSL:1 MANE Select	c.1533T>C	p.Ile511Ile	synonymous	Exon 12 of 12	ENSP00000298542.3
FRMD7	ENST00000464296.1	TSL:1	c.1488T>C	p.Ile496Ile	synonymous	Exon 12 of 12	ENSP00000417996.1
FRMD7	ENST00000370879.5	TSL:1	c.1173T>C	p.Ile391Ile	synonymous	Exon 8 of 8	ENSP00000359916.1

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

34812

AN:

110084

Hom.:

4442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.306

GnomAD2 exomes

AF:

0.260

AC:

47497

AN:

182804

AF XY:

0.260

show subpopulations

Gnomad AFR exome

AF:

0.441

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.291

AC:

319158

AN:

1097680

Hom.:

32808

Cov.:

AF XY:

0.288

AC XY:

104579

AN XY:

363080

show subpopulations

African (AFR)

AF:

0.439

AC:

11584

AN:

26395

American (AMR)

AF:

0.125

AC:

4388

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

5741

AN:

19383

East Asian (EAS)

AF:

0.0736

AC:

2222

AN:

30198

South Asian (SAS)

AF:

0.210

AC:

11357

AN:

54139

European-Finnish (FIN)

AF:

0.301

AC:

12214

AN:

40521

Middle Eastern (MID)

AF:

0.394

AC:

1629

AN:

4134

European-Non Finnish (NFE)

AF:

0.305

AC:

256614

AN:

841621

Other (OTH)

AF:

0.291

AC:

13409

AN:

46085

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

9740

19480

29221

38961

48701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8868

17736

26604

35472

44340

<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:

0.316

AC:

34838

AN:

110138

Hom.:

4446

Cov.:

AF XY:

0.295

AC XY:

9557

AN XY:

32434

show subpopulations

African (AFR)

AF:

0.428

AC:

12932

AN:

30182

American (AMR)

AF:

0.169

AC:

1745

AN:

10345

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

798

AN:

2622

East Asian (EAS)

AF:

0.0993

AC:

347

AN:

3496

South Asian (SAS)

AF:

0.198

AC:

509

AN:

2576

European-Finnish (FIN)

AF:

0.286

AC:

1662

AN:

5803

Middle Eastern (MID)

AF:

0.355

AC:

AN:

211

European-Non Finnish (NFE)

AF:

0.308

AC:

16224

AN:

52721

Other (OTH)

AF:

0.302

AC:

455

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

827

1654

2480

3307

4134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.302

Hom.:

17661

Bravo

AF:

0.313

EpiCase

AF:

0.305

EpiControl

AF:

0.303

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Nystagmus 1, congenital, X-linked (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.68

(source)

DANN

Benign

0.70

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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NM_194277.3:c.1533T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over