18-812712-C-G

Variant names:

• chr18-812712-C-G
• rs7233932
• ENST00000610185.3:n.336C>G

Variant summary

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

The ENST00000610185.3(ENSG00000273355):​n.336C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,058 control chromosomes in the GnomAD database, including 11,091 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 0.37 (11091 hom., cov: 32)
• Consequence: ENSG00000273355 ENST00000610185.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 2 publications found

Genes affected

ENSG00000273355 (HGNC:):

YES1 (HGNC:12841): (YES proto-oncogene 1, Src family tyrosine kinase) This gene is the cellular homolog of the Yamaguchi sarcoma virus oncogene. The encoded protein has tyrosine kinase activity and belongs to the src family of proteins. This gene lies in close proximity to thymidylate synthase gene on chromosome 18, and a corresponding pseudogene has been found on chromosome 22. [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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YES1	XM_024451244.2	c.-51G>C		5_prime_UTR_variant	Exon 1 of 12		XP_024307012.1
YES1	XM_047437770.1	c.-51G>C		5_prime_UTR_variant	Exon 1 of 11		XP_047293726.1
YES1	XM_024451243.2	c.-337G>C		upstream_gene_variant			XP_024307011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000273355	ENST00000610185.3	n.336C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000273355	ENST00000832908.1	n.79+188C>G		intron_variant	Intron 1 of 1
ENSG00000273355	ENST00000832909.1	n.28+188C>G		intron_variant	Intron 1 of 1
YES1	ENST00000584307.5	c.-337G>C		upstream_gene_variant		1		ENSP00000462468.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56345 AN: 151940 Hom.: 11081 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.371 AC: 56403 AN: 152058 Hom.: 11091 Cov.: 32 AF XY: 0.370 AC XY: 27472 AN XY: 74340

African (AFR) AF: 0.489 AC: 20273 AN: 41466

American (AMR) AF: 0.428 AC: 6541 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3470

East Asian (EAS) AF: 0.339 AC: 1747 AN: 5158

South Asian (SAS) AF: 0.385 AC: 1858 AN: 4822

European-Finnish (FIN) AF: 0.255 AC: 2700 AN: 10582

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21031 AN: 67972

Other (OTH) AF: 0.349 AC: 735 AN: 2108

Alfa AF: 0.342 Hom.: 1156

Bravo AF: 0.390

Asia WGS AF: 0.383 AC: 1335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.3
DANN	Benign	0.52
PhyloP100		-0.42
PromoterAI		-0.0055	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7233932; hg19: chr18-812713;