rs7631421

Variant names:

• chr3-69458148-G-C
• rs7631421
• ENST00000459638.5:c.-128-25387C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-69458148-G-C
• chr3-69458148-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000459638.5(FRMD4B):​c.-128-25387C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,090 control chromosomes in the GnomAD database, including 9,980 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 0.35 (9980 hom., cov: 32)
• Consequence: FRMD4B ENST00000459638.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4B	XM_017005991.2	c.-128-25387C>G		intron_variant	Intron 1 of 24		XP_016861480.1
FRMD4B	XM_047447767.1	c.-128-25387C>G		intron_variant	Intron 1 of 24		XP_047303723.1
FRMD4B	XM_017005993.2	c.-128-25387C>G		intron_variant	Intron 1 of 23		XP_016861482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000459638.5	c.-128-25387C>G		intron_variant	Intron 1 of 5	5		ENSP00000417550.1
FRMD4B	ENST00000497880.5	c.-128-25387C>G		intron_variant	Intron 1 of 4	4		ENSP00000417765.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53760 AN: 151972 Hom.: 9972 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.341

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.354 AC: 53787 AN: 152090 Hom.: 9980 Cov.: 32 AF XY: 0.351 AC XY: 26088 AN XY: 74328

African (AFR) AF: 0.462 AC: 19150 AN: 41486

American (AMR) AF: 0.315 AC: 4816 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3468

East Asian (EAS) AF: 0.301 AC: 1558 AN: 5168

South Asian (SAS) AF: 0.337 AC: 1625 AN: 4818

European-Finnish (FIN) AF: 0.293 AC: 3098 AN: 10562

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21653 AN: 67988

Other (OTH) AF: 0.345 AC: 728 AN: 2112

Alfa AF: 0.169 Hom.: 287

Bravo AF: 0.359

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.39
PhyloP100		0.042

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7631421; hg19: chr3-69507299;