rs1933739

Variant names:

• chr6-115987881-T-C
• rs1933739
• NM_002031.3:c.466+15996A>G

Variant summary

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

The NM_002031.3(FRK):​c.466+15996A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,928 control chromosomes in the GnomAD database, including 32,510 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 0.65 (32510 hom., cov: 32)
• Consequence: FRK NM_002031.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 3 publications found

Genes affected

FRK (HGNC:3955): (fyn related Src family tyrosine kinase) The protein encoded by this gene belongs to the TYR family of protein kinases. This tyrosine kinase is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. [provided by RefSeq, Jul 2008]

ENSG00000289376 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRK	NM_002031.3	c.466+15996A>G		intron_variant	Intron 2 of 7	ENST00000606080.2	NP_002022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRK	ENST00000606080.2	c.466+15996A>G		intron_variant	Intron 2 of 7	1	NM_002031.3	ENSP00000476145.1
ENSG00000289376	ENST00000692859.3	n.269-85703A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98519 AN: 151810 Hom.: 32484 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.649 AC: 98595 AN: 151928 Hom.: 32510 Cov.: 32 AF XY: 0.649 AC XY: 48167 AN XY: 74250

African (AFR) AF: 0.535 AC: 22180 AN: 41434

American (AMR) AF: 0.768 AC: 11702 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2554 AN: 3466

East Asian (EAS) AF: 0.831 AC: 4300 AN: 5174

South Asian (SAS) AF: 0.742 AC: 3581 AN: 4824

European-Finnish (FIN) AF: 0.592 AC: 6258 AN: 10572

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45754 AN: 67900

Other (OTH) AF: 0.683 AC: 1441 AN: 2110

Alfa AF: 0.683 Hom.: 22665

Bravo AF: 0.661

Asia WGS AF: 0.728 AC: 2535 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.46
DANN	Benign	0.45
PhyloP100		-1.4
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: rs1933739; hg19: chr6-116309044; COSMIC: COSV73384218;