6-111801023-C-T

Variant names:

• chr6-111801023-C-T
• rs2148710
• NM_002037.5:c.-81-20388G>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.-81-20388G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,174 control chromosomes in the GnomAD database, including 11,229 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 0.30 (11229 hom., cov: 32)
• Consequence: FYN NM_002037.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 18 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYN	NM_002037.5	MANE Select	c.-81-20388G>A		intron	N/A	NP_002028.1
	FYN	NM_153047.4		c.-81-20388G>A		intron	N/A	NP_694592.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYN	ENST00000354650.7	TSL:1 MANE Select	c.-81-20388G>A		intron	N/A	ENSP00000346671.3
	FYN	ENST00000912320.1		c.-81-20388G>A		intron	N/A	ENSP00000582379.1
	FYN	ENST00000912326.1		c.-82+17592G>A		intron	N/A	ENSP00000582385.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46080 AN: 152056 Hom.: 11187 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.303 AC: 46179 AN: 152174 Hom.: 11229 Cov.: 32 AF XY: 0.299 AC XY: 22230 AN XY: 74384

African (AFR) AF: 0.679 AC: 28193 AN: 41500

American (AMR) AF: 0.226 AC: 3454 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3470

East Asian (EAS) AF: 0.285 AC: 1474 AN: 5172

South Asian (SAS) AF: 0.198 AC: 953 AN: 4820

European-Finnish (FIN) AF: 0.0917 AC: 972 AN: 10604

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9620 AN: 67998

Other (OTH) AF: 0.294 AC: 621 AN: 2114

Alfa AF: 0.178 Hom.: 7756

Bravo AF: 0.330

Asia WGS AF: 0.249 AC: 866 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0030
DANN	Benign	0.62
PhyloP100		-2.1
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: rs2148710; hg19: chr6-112122226;