chr6-115942018-T-C

Variant names:

• chr6-115942018-T-C
• rs580396
• NM_002031.3:c.*396A>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.*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
• Publications: 13 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=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRK	NM_002031.3	MANE Select	c.*396A>G		3_prime_UTR	Exon 8 of 8	NP_002022.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRK	ENST00000606080.2	TSL:1 MANE Select	c.*396A>G		3_prime_UTR	Exon 8 of 8	ENSP00000476145.1
	ENSG00000289376	ENST00000692859.3		n.269-39840A>G		intron	N/A

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

African (AFR) AF: 0.410 AC: 55 AN: 134

American (AMR) AF: 0.542 AC: 948 AN: 1748

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 207 AN: 360

East Asian (EAS) AF: 0.859 AC: 507 AN: 590

South Asian (SAS) AF: 0.727 AC: 1839 AN: 2528

European-Finnish (FIN) AF: 0.694 AC: 937 AN: 1350

Middle Eastern (MID) AF: 0.600 AC: 30 AN: 50

European-Non Finnish (NFE) AF: 0.620 AC: 7230 AN: 11652

Other (OTH) AF: 0.634 AC: 583 AN: 920

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

African (AFR) AF: 0.535 AC: 22194 AN: 41452

American (AMR) AF: 0.562 AC: 8584 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2076 AN: 3472

East Asian (EAS) AF: 0.837 AC: 4331 AN: 5174

South Asian (SAS) AF: 0.743 AC: 3589 AN: 4830

European-Finnish (FIN) AF: 0.705 AC: 7449 AN: 10572

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42295 AN: 67966

Other (OTH) AF: 0.578 AC: 1220 AN: 2110

Alfa AF: 0.602 Hom.: 34321

Bravo AF: 0.590

Asia WGS AF: 0.774 AC: 2689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.0
DANN	Benign	0.87
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs580396; hg19: chr6-116263181;