3-69173712-T-G

Variant names:

• chr3-69173712-T-G
• rs4473559
• NM_015123.3:c.2985-1731A>C

Variant summary

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

The NM_015123.3(FRMD4B):​c.2985-1731A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,204 control chromosomes in the GnomAD database, including 61,505 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 0.89 (61505 hom., cov: 33)
• Consequence: FRMD4B NM_015123.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4B	NM_015123.3	c.2985-1731A>C		intron_variant	Intron 22 of 22	ENST00000398540.8	NP_055938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000398540.8	c.2985-1731A>C		intron_variant	Intron 22 of 22	1	NM_015123.3	ENSP00000381549.3
FRMD4B	ENST00000478263.5	c.1941-1731A>C		intron_variant	Intron 12 of 12	1		ENSP00000418682.1

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134976 AN: 152086 Hom.: 61485 Cov.: 33

Gnomad AFR AF: 0.683

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.956

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.913

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

GnomAD4 genome AF: 0.887 AC: 135039 AN: 152204 Hom.: 61505 Cov.: 33 AF XY: 0.884 AC XY: 65766 AN XY: 74428

African (AFR) AF: 0.682 AC: 28310 AN: 41494

American (AMR) AF: 0.956 AC: 14622 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3442 AN: 3470

East Asian (EAS) AF: 0.656 AC: 3388 AN: 5168

South Asian (SAS) AF: 0.820 AC: 3958 AN: 4824

European-Finnish (FIN) AF: 0.995 AC: 10552 AN: 10608

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.994 AC: 67646 AN: 68034

Other (OTH) AF: 0.913 AC: 1929 AN: 2112

Alfa AF: 0.955 Hom.: 195385

Bravo AF: 0.876

Asia WGS AF: 0.788 AC: 2740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.64
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

Publications

LitVar

Other links and lift over

dbSNP: rs4473559; hg19: chr3-69222863;