rs6916861

Positions:

• chr6-111661054-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002037.5(FYN):​c.*685T>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 0.193 in 152,026 control chromosomes in the GnomAD database, including 3,631 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 0.19 (3631 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: FYN NM_002037.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FYN	NM_002037.5	c.*685T>G		3_prime_UTR_variant	14/14	ENST00000354650.7	NP_002028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FYN	ENST00000354650.7	c.*685T>G		3_prime_UTR_variant	14/14	1	NM_002037.5	ENSP00000346671	P3
FYN	ENST00000368682.8	c.*685T>G		3_prime_UTR_variant	14/14	5		ENSP00000357671	A1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29240 AN: 151900 Hom.: 3625 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 EAS exome AF: 0.250

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.193 AC: 29265 AN: 152018 Hom.: 3631 Cov.: 32 AF XY: 0.191 AC XY: 14168 AN XY: 74318

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.0572

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.153

Alfa AF: 0.137 Hom.: 3199

Bravo AF: 0.202

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs6916861; hg19: chr6-111982257;