18-722402-T-C

Variant names:

• chr18-722402-T-C
• rs1060922
• NM_005433.4:c.*2022A>G

Variant summary

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

The NM_005433.4(YES1):​c.*2022A>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 0.463 in 152,476 control chromosomes in the GnomAD database, including 16,600 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 0.46 (16561 hom., cov: 32)
  • Exomes 𝑓: 0.44 (39 hom.)
• Consequence: YES1 NM_005433.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

Genes affected

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YES1	NM_005433.4	c.*2022A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000314574.5	NP_005424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YES1	ENST00000314574	c.*2022A>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_005433.4	ENSP00000324740.4
YES1	ENST00000584307	c.*2022A>G		3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000462468.1
YES1	ENST00000577961	c.*2022A>G		3_prime_UTR_variant	Exon 12 of 12	5		ENSP00000464380.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70360 AN: 151926 Hom.: 16552 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.438 AC: 189 AN: 432 Hom.: 39 Cov.: 0 AF XY: 0.469 AC XY: 122 AN XY: 260

Gnomad4 FIN exome AF: 0.434

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.463 AC: 70422 AN: 152044 Hom.: 16561 Cov.: 32 AF XY: 0.465 AC XY: 34582 AN XY: 74342

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.430

Alfa AF: 0.418 Hom.: 16579

Bravo AF: 0.470

Asia WGS AF: 0.488 AC: 1698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1060922; hg19: chr18-722402;