18-722402-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005433.4. 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
	YES1	NM_005433.4	MANE Select	c.*2022A>G		3_prime_UTR	Exon 12 of 12	NP_005424.1	P07947

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YES1	ENST00000314574.5	TSL:1 MANE Select	c.*2022A>G		3_prime_UTR	Exon 12 of 12	ENSP00000324740.4	P07947
	YES1	ENST00000584307.5	TSL:1	c.*2022A>G		3_prime_UTR	Exon 12 of 12	ENSP00000462468.1	P07947
	YES1	ENST00000577961.5	TSL:5	c.*2022A>G		3_prime_UTR	Exon 12 of 12	ENSP00000464380.1	J3QRU1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.434 AC: 185 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.545 AC: 22601 AN: 41450

American (AMR) AF: 0.501 AC: 7648 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3472

East Asian (EAS) AF: 0.430 AC: 2219 AN: 5166

South Asian (SAS) AF: 0.498 AC: 2398 AN: 4820

European-Finnish (FIN) AF: 0.437 AC: 4627 AN: 10588

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28265 AN: 67966

Other (OTH) AF: 0.430 AC: 908 AN: 2110

Alfa AF: 0.431 Hom.: 31249

Bravo AF: 0.470

Asia WGS AF: 0.488 AC: 1698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.49
PhyloP100		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1060922; hg19: chr18-722402;