6-115942018-T-C

Position:

• chr6-115942018-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.*396A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 171,382 control chromosomes in the GnomAD database, including 32,785 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 0.61 (28648 hom., cov: 32)
  • Exomes 𝑓: 0.64 (4137 hom.)
• Consequence: FRK NM_002031.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRK	NM_002031.3	c.*396A>G		3_prime_UTR_variant	8/8	ENST00000606080.2	NP_002022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRK	ENST00000606080	c.*396A>G		3_prime_UTR_variant	8/8	1	NM_002031.3	ENSP00000476145.1
ENSG00000289376	ENST00000692859.2	n.223-39840A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92616 AN: 151932 Hom.: 28631 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.575

GnomAD4 exome AF: 0.638 AC: 12336 AN: 19332 Hom.: 4137 Cov.: 0 AF XY: 0.647 AC XY: 6733 AN XY: 10412

Gnomad4 AFR exome AF: 0.410

Gnomad4 AMR exome AF: 0.542

Gnomad4 ASJ exome AF: 0.575

Gnomad4 EAS exome AF: 0.859

Gnomad4 SAS exome AF: 0.727

Gnomad4 FIN exome AF: 0.694

Gnomad4 NFE exome AF: 0.620

Gnomad4 OTH exome AF: 0.634

GnomAD4 genome AF: 0.610 AC: 92679 AN: 152050 Hom.: 28648 Cov.: 32 AF XY: 0.617 AC XY: 45833 AN XY: 74322

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.837

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.578

Alfa AF: 0.606 Hom.: 26440

Bravo AF: 0.590

Asia WGS AF: 0.774 AC: 2689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.0
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs580396; hg19: chr6-116263181;