6-111661054-A-C

Variant names:

• chr6-111661054-A-C
• rs6916861
• NM_002037.5:c.*685T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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 (AFR) allele frequency at 95% confidence interval = 0.341 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.*685T>G		3_prime_UTR	Exon 14 of 14	NP_002028.1
	FYN	NM_001370529.1		c.*685T>G		3_prime_UTR	Exon 12 of 12	NP_001357458.1
	FYN	NM_153047.4		c.*685T>G		3_prime_UTR	Exon 14 of 14	NP_694592.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYN	ENST00000354650.7	TSL:1 MANE Select	c.*685T>G		3_prime_UTR	Exon 14 of 14	ENSP00000346671.3
	FYN	ENST00000368682.8	TSL:5	c.*685T>G		3_prime_UTR	Exon 14 of 14	ENSP00000357671.3
	FYN	ENST00000229471.8	TSL:1	c.*685T>G		downstream_gene	N/A	ENSP00000229471.4

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.346 AC: 14321 AN: 41388

American (AMR) AF: 0.131 AC: 2006 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1539 AN: 5176

South Asian (SAS) AF: 0.0572 AC: 276 AN: 4822

European-Finnish (FIN) AF: 0.125 AC: 1318 AN: 10574

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8889 AN: 67996

Other (OTH) AF: 0.153 AC: 323 AN: 2110

Alfa AF: 0.148 Hom.: 8323

Bravo AF: 0.202

Asia WGS AF: 0.181 AC: 628 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	4.4
DANN	Benign	0.72
PhyloP100		0.61
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: rs6916861; hg19: chr6-111982257;