rs9400504

Variant names:

• chr6-111785089-C-T
• rs9400504
• NM_002037.5:c.-81-4454G>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.-81-4454G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,022 control chromosomes in the GnomAD database, including 14,971 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 0.44 (14971 hom., cov: 32)
• Consequence: FYN NM_002037.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYN	NM_002037.5	c.-81-4454G>A		intron_variant	Intron 2 of 13	ENST00000354650.7	NP_002028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYN	ENST00000354650.7	c.-81-4454G>A		intron_variant	Intron 2 of 13	1	NM_002037.5	ENSP00000346671.3

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66654 AN: 151904 Hom.: 14979 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.439 AC: 66669 AN: 152022 Hom.: 14971 Cov.: 32 AF XY: 0.443 AC XY: 32884 AN XY: 74292

African (AFR) AF: 0.377 AC: 15640 AN: 41456

American (AMR) AF: 0.556 AC: 8488 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1474 AN: 3472

East Asian (EAS) AF: 0.696 AC: 3593 AN: 5164

South Asian (SAS) AF: 0.508 AC: 2447 AN: 4814

European-Finnish (FIN) AF: 0.412 AC: 4354 AN: 10568

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29222 AN: 67950

Other (OTH) AF: 0.493 AC: 1043 AN: 2114

Alfa AF: 0.423 Hom.: 3085

Bravo AF: 0.451

Asia WGS AF: 0.544 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.36
PhyloP100		-1.5
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: rs9400504; hg19: chr6-112106292;