rs12527159

Variant names:

• chr6-116076619-A-T
• rs12527159
• ENST00000692859.3:n.268+23873T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000692859.3(ENSG00000289376):​n.268+23873T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,130 control chromosomes in the GnomAD database, including 2,892 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 0.18 (2892 hom., cov: 33)
• Consequence: ENSG00000289376 ENST00000692859.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 1 publications found

Genes affected

ENSG00000289376 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRK	XM_011535654.3	c.-286-16022T>A		intron_variant	Intron 1 of 8		XP_011533956.1
FRK	XM_011535655.3	c.-283-16025T>A		intron_variant	Intron 1 of 8		XP_011533957.1
FRK	XM_011535656.3	c.5+23873T>A		intron_variant	Intron 1 of 7		XP_011533958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289376	ENST00000692859.3	n.268+23873T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27117 AN: 152014 Hom.: 2887 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.178 AC: 27152 AN: 152130 Hom.: 2892 Cov.: 33 AF XY: 0.180 AC XY: 13396 AN XY: 74350

African (AFR) AF: 0.291 AC: 12088 AN: 41476

American (AMR) AF: 0.202 AC: 3080 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3472

East Asian (EAS) AF: 0.0396 AC: 205 AN: 5180

South Asian (SAS) AF: 0.190 AC: 918 AN: 4824

European-Finnish (FIN) AF: 0.177 AC: 1876 AN: 10578

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7920 AN: 67998

Other (OTH) AF: 0.163 AC: 345 AN: 2114

Alfa AF: 0.153 Hom.: 256

Bravo AF: 0.188

Asia WGS AF: 0.143 AC: 496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.29
PhyloP100		-0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12527159; hg19: chr6-116397782; COSMIC: COSV60271292;