rs62254461

Positions:

• chr3-69221881-G-A
• chr3-69221881-G-C
• chr3-69221881-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_015123.3(FRMD4B):​c.708C>T​(p.Leu236Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0964 in 1,566,174 control chromosomes in the GnomAD database, including 8,387 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 0.079 (645 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7742 hom.)
• Consequence: FRMD4B NM_015123.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.822

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]

FRMD4B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=0.822 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD4B	NM_015123.3	c.708C>T	p.Leu236Leu	synonymous_variant	9/23	ENST00000398540.8	NP_055938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000398540.8	c.708C>T	p.Leu236Leu	synonymous_variant	9/23	1	NM_015123.3	ENSP00000381549.3

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 12017 AN: 152128 Hom.: 645 Cov.: 32

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0782

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0837

GnomAD3 exomes AF: 0.0863 AC: 19629 AN: 227536 Hom.: 1092 AF XY: 0.0891 AC XY: 10893 AN XY: 122240

Gnomad AFR exome AF: 0.0171

Gnomad AMR exome AF: 0.0564

Gnomad ASJ exome AF: 0.162

Gnomad EAS exome AF: 0.000120

Gnomad SAS exome AF: 0.0463

Gnomad FIN exome AF: 0.0991

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.0971

GnomAD4 exome AF: 0.0983 AC: 138966 AN: 1413928 Hom.: 7742 Cov.: 25 AF XY: 0.0976 AC XY: 68683 AN XY: 703832

Gnomad4 AFR exome AF: 0.0163

Gnomad4 AMR exome AF: 0.0605

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.000153

Gnomad4 SAS exome AF: 0.0474

Gnomad4 FIN exome AF: 0.0988

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.0890

GnomAD4 genome AF: 0.0789 AC: 12011 AN: 152246 Hom.: 645 Cov.: 32 AF XY: 0.0780 AC XY: 5804 AN XY: 74440

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.0781

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0395

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0829

Alfa AF: 0.102 Hom.: 512

Bravo AF: 0.0755

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.3
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs62254461; hg19: chr3-69271032; COSMIC: COSV68333976; COSMIC: COSV68333976;