rs1933737

chr6-115989124-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRK	NM_002031.3	c.466+14753A>G		intron_variant		ENST00000606080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRK	ENST00000606080.2	c.466+14753A>G		intron_variant		1	NM_002031.3	P1
	ENST00000692859.2	n.223-86946A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.0185

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.301

Alfa AF: 0.297 Hom.: 1090

Bravo AF: 0.285

Asia WGS AF: 0.111 AC: 390 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.2
Dann	Benign	0.39

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: rs1933737; hg19: chr6-116310287; COSMIC: COSV73383888;