3-69189939-G-A

Position:

• chr3-69189939-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015123.3(FRMD4B):​c.1728C>T​(p.Pro576=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 1,592,604 control chromosomes in the GnomAD database, including 307 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 0.025 (176 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (131 hom.)
• Consequence: FRMD4B NM_015123.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.145 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD4B	NM_015123.3	c.1728C>T	p.Pro576=	synonymous_variant	18/23	ENST00000398540.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD4B	ENST00000398540.8	c.1728C>T	p.Pro576=	synonymous_variant	18/23	1	NM_015123.3	P1
FRMD4B	ENST00000478263.5	c.684C>T	p.Pro228=	synonymous_variant	8/13	1

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3782 AN: 152114 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0873

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00602 AC: 1498 AN: 249008 Hom.: 60 AF XY: 0.00466 AC XY: 629 AN XY: 135106

Gnomad AFR exome AF: 0.0871

Gnomad AMR exome AF: 0.00311

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000257

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00247 AC: 3558 AN: 1440372 Hom.: 131 Cov.: 25 AF XY: 0.00206 AC XY: 1479 AN XY: 717990

Gnomad4 AFR exome AF: 0.0881

Gnomad4 AMR exome AF: 0.00347

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000210

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000141

Gnomad4 OTH exome AF: 0.00521

GnomAD4 genome AF: 0.0249 AC: 3791 AN: 152232 Hom.: 176 Cov.: 32 AF XY: 0.0241 AC XY: 1792 AN XY: 74438

Gnomad4 AFR AF: 0.0873

Gnomad4 AMR AF: 0.00785

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0109 Hom.: 29

Bravo AF: 0.0283

Asia WGS AF: 0.00462 AC: 16 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.2
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs61737524; hg19: chr3-69239090;