rs922948

Positions:

• chr3-69393486-G-A
• chr3-69393486-G-C
• chr3-69393486-G-T

Variant summary

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

The ENST00000497880.5(FRMD4B):​c.-1+39148C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,066 control chromosomes in the GnomAD database, including 34,669 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 0.67 (34669 hom., cov: 31)
• Consequence: FRMD4B ENST00000497880.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780

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]

FRMD4B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD4B	XM_017005991.2	c.-1+39148C>T		intron_variant			XP_016861480.1
FRMD4B	XM_047447767.1	c.-1+39148C>T		intron_variant			XP_047303723.1
FRMD4B	XM_017005993.2	c.-1+39148C>T		intron_variant			XP_016861482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000459638.5	c.-1+39148C>T		intron_variant		5		ENSP00000417550.1
FRMD4B	ENST00000497880.5	c.-1+39148C>T		intron_variant		4		ENSP00000417765.1
FRMD4B	ENST00000497757.1	n.271+39148C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102403 AN: 151946 Hom.: 34630 Cov.: 31

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.674 AC: 102500 AN: 152066 Hom.: 34669 Cov.: 31 AF XY: 0.675 AC XY: 50193 AN XY: 74336

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.667

Alfa AF: 0.686 Hom.: 42013

Bravo AF: 0.672

Asia WGS AF: 0.653 AC: 2274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs922948; hg19: chr3-69442637;