3-69524251-T-C

Position:

• chr3-69524251-T-C

Variant summary

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

The ENST00000497880.5(FRMD4B):​c.-129+16904A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,126 control chromosomes in the GnomAD database, including 6,369 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 0.28 (6369 hom., cov: 32)
• Consequence: FRMD4B ENST00000497880.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD4B	XM_017005991.2	c.-129+16904A>G		intron_variant			XP_016861480.1
FRMD4B	XM_047447767.1	c.-129+17955A>G		intron_variant			XP_047303723.1
FRMD4B	XM_017005993.2	c.-129+17955A>G		intron_variant			XP_016861482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000459638.5	c.-129+17955A>G		intron_variant		5		ENSP00000417550.1
FRMD4B	ENST00000497880.5	c.-129+16904A>G		intron_variant		4		ENSP00000417765.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43295 AN: 152008 Hom.: 6370 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.285 AC: 43308 AN: 152126 Hom.: 6369 Cov.: 32 AF XY: 0.284 AC XY: 21104 AN XY: 74366

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.266

Alfa AF: 0.286 Hom.: 4268

Bravo AF: 0.274

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1391769; hg19: chr3-69573402;