chr3-69221881-G-A

Variant names:

• chr3-69221881-G-A
• rs62254461
• NM_015123.3:c.708C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015123.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4B	NM_015123.3	MANE Select	c.708C>T	p.Leu236Leu	synonymous	Exon 9 of 23	NP_055938.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4B	ENST00000398540.8	TSL:1 MANE Select	c.708C>T	p.Leu236Leu	synonymous	Exon 9 of 23	ENSP00000381549.3
	FRMD4B	ENST00000493880.5	TSL:4	c.381C>T	p.Leu127Leu	synonymous	Exon 6 of 8	ENSP00000418962.1
	FRMD4B	ENST00000470070.6	TSL:5	n.602C>T		non_coding_transcript_exon	Exon 9 of 12

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

GnomAD2 exomes AF: 0.0863 AC: 19629 AN: 227536 AF XY: 0.0891

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 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

African (AFR) AF: 0.0163 AC: 533 AN: 32796

American (AMR) AF: 0.0605 AC: 2580 AN: 42634

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 4119 AN: 25532

East Asian (EAS) AF: 0.000153 AC: 6 AN: 39288

South Asian (SAS) AF: 0.0474 AC: 3922 AN: 82746

European-Finnish (FIN) AF: 0.0988 AC: 5210 AN: 52710

Middle Eastern (MID) AF: 0.109 AC: 622 AN: 5692

European-Non Finnish (NFE) AF: 0.109 AC: 116734 AN: 1073676

Other (OTH) AF: 0.0890 AC: 5240 AN: 58854

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

African (AFR) AF: 0.0204 AC: 848 AN: 41560

American (AMR) AF: 0.0781 AC: 1194 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0395 AC: 191 AN: 4830

European-Finnish (FIN) AF: 0.101 AC: 1070 AN: 10580

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7853 AN: 68018

Other (OTH) AF: 0.0829 AC: 175 AN: 2112

Alfa AF: 0.0900 Hom.: 776

Bravo AF: 0.0755

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.3
DANN	Benign	0.70
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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