rs13059488

chr3-69197001-A-Gchr3-69197001-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015123.3(FRMD4B):c.991T>C(p.Leu331=) variant causes a synonymous change. The variant allele was found at a frequency of 0.911 in 1,607,080 control chromosomes in the GnomAD database, including 675,649 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (53705 hom., cov: 32)
  • Exomes 𝑓: 0.92 (621944 hom.)
• Consequence: FRMD4B NM_015123.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79

Genes affected

FRMD4B (HGNC:24886): (FERM domain containing 4B) This gene encodes a GRP1-binding protein which contains a FERM protein interaction domain as well as two coiled coil domains. This protein may play a role as a scaffolding protein. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD4B	NM_015123.3	c.991T>C	p.Leu331=	synonymous_variant	13/23	ENST00000398540.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD4B	ENST00000398540.8	c.991T>C	p.Leu331=	synonymous_variant	13/23	1	NM_015123.3	P1

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124981 AN: 152082 Hom.: 53689 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.859

GnomAD3 exomes AF: 0.881 AC: 218908 AN: 248548 Hom.: 98327 AF XY: 0.883 AC XY: 119078 AN XY: 134858

Gnomad AFR exome AF: 0.557

Gnomad AMR exome AF: 0.945

Gnomad ASJ exome AF: 0.951

Gnomad EAS exome AF: 0.626

Gnomad SAS exome AF: 0.797

Gnomad FIN exome AF: 0.952

Gnomad NFE exome AF: 0.947

Gnomad OTH exome AF: 0.917

GnomAD4 exome AF: 0.920 AC: 1339192 AN: 1454880 Hom.: 621944 Cov.: 29 AF XY: 0.918 AC XY: 664717 AN XY: 724152

Gnomad4 AFR exome AF: 0.545

Gnomad4 AMR exome AF: 0.942

Gnomad4 ASJ exome AF: 0.949

Gnomad4 EAS exome AF: 0.629

Gnomad4 SAS exome AF: 0.797

Gnomad4 FIN exome AF: 0.952

Gnomad4 NFE exome AF: 0.950

Gnomad4 OTH exome AF: 0.896

GnomAD4 genome AF: 0.822 AC: 125039 AN: 152200 Hom.: 53705 Cov.: 32 AF XY: 0.820 AC XY: 61007 AN XY: 74414

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.946

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.792

Gnomad4 FIN AF: 0.954

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.860

Alfa AF: 0.886 Hom.: 33753

Bravo AF: 0.807

Asia WGS AF: 0.762 AC: 2651 AN: 3478

EpiCase AF: 0.947

EpiControl AF: 0.947

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	12
Dann	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs13059488; hg19: chr3-69246152; COSMIC: COSV68330108; COSMIC: COSV68330108;