6-115989124-T-C

Variant names:

• chr6-115989124-T-C
• rs1933737
• NM_002031.3:c.466+14753A>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+14753A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,676 control chromosomes in the GnomAD database, including 6,330 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 (6330 hom., cov: 32)
• Consequence: FRK NM_002031.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002031.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRK	NM_002031.3	MANE Select	c.466+14753A>G		intron	N/A	NP_002022.1	P42685-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRK	ENST00000606080.2	TSL:1 MANE Select	c.466+14753A>G		intron	N/A	ENSP00000476145.1	P42685-1
	FRK	ENST00000891227.1		c.466+14753A>G		intron	N/A	ENSP00000561286.1
	FRK	ENST00000891226.1		c.466+14753A>G		intron	N/A	ENSP00000561285.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42505 AN: 151558 Hom.: 6325 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.280 AC: 42537 AN: 151676 Hom.: 6330 Cov.: 32 AF XY: 0.272 AC XY: 20140 AN XY: 74146

African (AFR) AF: 0.289 AC: 11988 AN: 41420

American (AMR) AF: 0.249 AC: 3783 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1240 AN: 3460

East Asian (EAS) AF: 0.0185 AC: 96 AN: 5182

South Asian (SAS) AF: 0.184 AC: 887 AN: 4810

European-Finnish (FIN) AF: 0.229 AC: 2421 AN: 10568

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21253 AN: 67734

Other (OTH) AF: 0.301 AC: 632 AN: 2102

Alfa AF: 0.292 Hom.: 2679

Bravo AF: 0.285

Asia WGS AF: 0.111 AC: 390 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.39
PhyloP100		-0.014
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: rs1933737; hg19: chr6-116310287; COSMIC: COSV73383888;