NM_002031.3:c.466+11624T>C

Variant names:

• chr6-115992253-A-G
• rs9384970
• NM_002031.3:c.466+11624T>C

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+11624T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 151,528 control chromosomes in the GnomAD database, including 45,845 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 0.77 (45845 hom., cov: 32)
• Consequence: FRK NM_002031.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRK	NM_002031.3	c.466+11624T>C		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+11624T>C		intron_variant	Intron 2 of 7	1	NM_002031.3	ENSP00000476145.1
ENSG00000289376	ENST00000692859.3	n.269-90075T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 116745 AN: 151410 Hom.: 45817 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.801

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

GnomAD4 genome AF: 0.771 AC: 116817 AN: 151528 Hom.: 45845 Cov.: 32 AF XY: 0.773 AC XY: 57257 AN XY: 74054

African (AFR) AF: 0.612 AC: 25321 AN: 41396

American (AMR) AF: 0.858 AC: 13053 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3011 AN: 3460

East Asian (EAS) AF: 0.884 AC: 4577 AN: 5176

South Asian (SAS) AF: 0.816 AC: 3934 AN: 4824

European-Finnish (FIN) AF: 0.832 AC: 8785 AN: 10564

Middle Eastern (MID) AF: 0.877 AC: 256 AN: 292

European-Non Finnish (NFE) AF: 0.819 AC: 55377 AN: 67590

Other (OTH) AF: 0.801 AC: 1684 AN: 2102

Alfa AF: 0.806 Hom.: 55708

Bravo AF: 0.770

Asia WGS AF: 0.831 AC: 2881 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.49
PhyloP100		-0.34
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: rs9384970; hg19: chr6-116313416; COSMIC: COSV73384223;