3-69385716-T-G

Position:

• chr3-69385716-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015123.3(FRMD4B):​c.162+112A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 916,916 control chromosomes in the GnomAD database, including 2,882 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 0.066 (507 hom., cov: 32)
  • Exomes 𝑓: 0.069 (2375 hom.)
• Consequence: FRMD4B NM_015123.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD4B	NM_015123.3	c.162+112A>C		intron_variant		ENST00000398540.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD4B	ENST00000398540.8	c.162+112A>C		intron_variant		1	NM_015123.3	P1

Frequencies

GnomAD3 genomes AF: 0.0659 AC: 10018 AN: 152118 Hom.: 505 Cov.: 32

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0611

Gnomad OTH AF: 0.0798

GnomAD4 exome AF: 0.0686 AC: 52445 AN: 764680 Hom.: 2375 AF XY: 0.0710 AC XY: 27063 AN XY: 381034

Gnomad4 AFR exome AF: 0.0223

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.0771

Gnomad4 EAS exome AF: 0.0856

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.0423

Gnomad4 NFE exome AF: 0.0605

Gnomad4 OTH exome AF: 0.0805

GnomAD4 genome AF: 0.0659 AC: 10032 AN: 152236 Hom.: 507 Cov.: 32 AF XY: 0.0693 AC XY: 5160 AN XY: 74426

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.0432

Gnomad4 NFE AF: 0.0611

Gnomad4 OTH AF: 0.0790

Alfa AF: 0.0626 Hom.: 375

Bravo AF: 0.0703

Asia WGS AF: 0.141 AC: 488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.94
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs17005789; hg19: chr3-69434867; COSMIC: COSV68332820;