dbSNP rs1057515770: FRMD7:c.*196G>C (chrX-132077676-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_194277.3(FRMD7):c.*196G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000045 in 555,388 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000043 ( 0 hom. 4 hem. )

Consequence

FRMD7
NM_194277.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.48

Publications

0 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BS2

High Hemizygotes in GnomAdExome4 at 4 XL gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD7	NM_194277.3	MANE Select	c.*196G>C		3_prime_UTR	Exon 12 of 12	NP_919253.1	Q6ZUT3-1
	FRMD7	NM_001306193.2		c.*196G>C		3_prime_UTR	Exon 12 of 12	NP_001293122.1	Q6ZUT3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FRMD7	ENST00000298542.9	TSL:1 MANE Select	c.*196G>C	3_prime_UTR	Exon 12 of 12	ENSP00000298542.3	Q6ZUT3-1
FRMD7	ENST00000370879.5	TSL:1	c.*196G>C	3_prime_UTR	Exon 8 of 8	ENSP00000359916.1	X6R7S7
FRMD7	ENST00000464296.1	TSL:1	c.*196G>C	downstream_gene	N/A	ENSP00000417996.1	Q6ZUT3-2

Frequencies

GnomAD3 genomes

AF:

0.0000536

AC:

AN:

111867

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000941

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000428

AC:

AN:

443521

Hom.:

Cov.:

AF XY:

0.0000310

AC XY:

AN XY:

128851

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11794

American (AMR)

AF:

0.00

AC:

AN:

15777

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10734

East Asian (EAS)

AF:

0.00

AC:

AN:

23421

South Asian (SAS)

AF:

0.00

AC:

AN:

28946

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28319

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1550

European-Non Finnish (NFE)

AF:

0.0000634

AC:

AN:

299663

Other (OTH)

AF:

0.00

AC:

AN:

23317

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000536

AC:

AN:

111867

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34039

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30819

American (AMR)

AF:

0.00

AC:

AN:

10506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3562

South Asian (SAS)

AF:

0.00

AC:

AN:

2687

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6105

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000941

AC:

AN:

53120

Other (OTH)

AF:

0.00

AC:

AN:

1492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nystagmus 1, congenital, X-linked (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.19

(source)

DANN

Benign

0.39

PhyloP100

-1.5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over