NM_002031.3:c.466+12147T>A

Variant names:

• chr6-115991730-A-T
• rs9488822
• NM_002031.3:c.466+12147T>A

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+12147T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,304 control chromosomes in the GnomAD database, including 9,289 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 0.35 (9289 hom., cov: 31)
• Consequence: FRK NM_002031.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 59 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRK	NM_002031.3	c.466+12147T>A		intron_variant	Intron 2 of 7	ENST00000606080.2	NP_002022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRK	ENST00000606080.2	c.466+12147T>A		intron_variant	Intron 2 of 7	1	NM_002031.3	ENSP00000476145.1
ENSG00000289376	ENST00000692859.3	n.269-89552T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52447 AN: 151186 Hom.: 9276 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.347 AC: 52500 AN: 151304 Hom.: 9289 Cov.: 31 AF XY: 0.343 AC XY: 25320 AN XY: 73922

African (AFR) AF: 0.367 AC: 15178 AN: 41338

American (AMR) AF: 0.410 AC: 6212 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1449 AN: 3456

East Asian (EAS) AF: 0.149 AC: 770 AN: 5166

South Asian (SAS) AF: 0.250 AC: 1207 AN: 4822

European-Finnish (FIN) AF: 0.311 AC: 3278 AN: 10530

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23366 AN: 67526

Other (OTH) AF: 0.375 AC: 787 AN: 2098

Alfa AF: 0.343 Hom.: 1105

Bravo AF: 0.361

Asia WGS AF: 0.216 AC: 751 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.2
DANN	Benign	0.57
PhyloP100		-0.67
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: rs9488822; hg19: chr6-116312893;