chr6-111760532-C-T

Variant names:

• chr6-111760532-C-T
• rs6914091
• NM_002037.5:c.-12+20034G>A

Variant summary

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

The NM_002037.5(FYN):​c.-12+20034G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,020 control chromosomes in the GnomAD database, including 16,529 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 0.46 (16529 hom., cov: 32)
• Consequence: FYN NM_002037.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 5 publications found

Genes affected

FYN (HGNC:4037): (FYN proto-oncogene, Src family tyrosine kinase) This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002037.5. 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
	FYN	NM_002037.5	MANE Select	c.-12+20034G>A		intron	N/A	NP_002028.1
	FYN	NM_153047.4		c.-12+20034G>A		intron	N/A	NP_694592.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYN	ENST00000354650.7	TSL:1 MANE Select	c.-12+20034G>A		intron	N/A	ENSP00000346671.3
	FYN	ENST00000368667.6	TSL:5	c.-12+20034G>A		intron	N/A	ENSP00000357656.2
	FYN	ENST00000368678.8	TSL:5	c.-11-40470G>A		intron	N/A	ENSP00000357667.4

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70384 AN: 151902 Hom.: 16509 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.463 AC: 70457 AN: 152020 Hom.: 16529 Cov.: 32 AF XY: 0.468 AC XY: 34798 AN XY: 74314

African (AFR) AF: 0.467 AC: 19369 AN: 41444

American (AMR) AF: 0.550 AC: 8413 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1504 AN: 3470

East Asian (EAS) AF: 0.616 AC: 3169 AN: 5144

South Asian (SAS) AF: 0.555 AC: 2677 AN: 4824

European-Finnish (FIN) AF: 0.430 AC: 4540 AN: 10554

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29231 AN: 67986

Other (OTH) AF: 0.515 AC: 1084 AN: 2106

Alfa AF: 0.442 Hom.: 8754

Bravo AF: 0.475

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.60
PhyloP100		-0.36
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: rs6914091; hg19: chr6-112081735; COSMIC: COSV57620890; COSMIC: COSV57620890;