ENST00000478263.5:c.-54T>C

Variant names:

• chr3-69197001-A-G
• rs13059488
• ENST00000478263.5:c.-54T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000478263.5(FRMD4B):​c.-54T>C variant causes a 5 prime UTR premature start codon gain 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 ENST00000478263.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FRMD4B	NM_015123.3	c.991T>C	p.Leu331Leu	synonymous_variant	Exon 13 of 23	ENST00000398540.8	NP_055938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000398540.8	c.991T>C	p.Leu331Leu	synonymous_variant	Exon 13 of 23	1	NM_015123.3	ENSP00000381549.3

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

GnomAD2 exomes AF: 0.881 AC: 218908 AN: 248548 AF XY: 0.883

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 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

African (AFR) AF: 0.545 AC: 18150 AN: 33294

American (AMR) AF: 0.942 AC: 42043 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 24767 AN: 26088

East Asian (EAS) AF: 0.629 AC: 24921 AN: 39628

South Asian (SAS) AF: 0.797 AC: 68464 AN: 85940

European-Finnish (FIN) AF: 0.952 AC: 50822 AN: 53382

Middle Eastern (MID) AF: 0.915 AC: 5279 AN: 5768

European-Non Finnish (NFE) AF: 0.950 AC: 1050861 AN: 1106018

Other (OTH) AF: 0.896 AC: 53885 AN: 60142

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

African (AFR) AF: 0.559 AC: 23195 AN: 41472

American (AMR) AF: 0.914 AC: 13983 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 3286 AN: 3472

East Asian (EAS) AF: 0.630 AC: 3260 AN: 5174

South Asian (SAS) AF: 0.792 AC: 3823 AN: 4828

European-Finnish (FIN) AF: 0.954 AC: 10116 AN: 10600

Middle Eastern (MID) AF: 0.911 AC: 266 AN: 292

European-Non Finnish (NFE) AF: 0.947 AC: 64442 AN: 68034

Other (OTH) AF: 0.860 AC: 1818 AN: 2114

Alfa AF: 0.883 Hom.: 33874

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
PhyloP100		5.8
Mutation Taster		=186/114	polymorphism

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

Other links and lift over

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