X-49606175-C-A

Position:

• chrX-49606175-C-A

Variant summary

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

The NM_001040663.4(GAGE1):​c.*160C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 297,463 control chromosomes in the GnomAD database, including 30,815 homozygotes. There are 42,522 hemizygotes in GnomAD. 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 0.44 (9041 hom., 13615 hem., cov: 22)
  • Exomes 𝑓: 0.56 (21774 hom. 28907 hem.)
• Consequence: GAGE1 NM_001040663.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

Genes affected

GAGE1 (HGNC:4098): (G antigen 1) This gene belongs to a family of genes that are expressed in a variety of tumors but not in normal tissues, except for the testis. The sequences of the family members are highly related but differ by scattered nucleotide substitutions. The antigenic peptide YRPRPRRY, which is also encoded by several other family members, is recognized by autologous cytolytic T lymphocytes. Nothing is presently known about the function of this protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAGE1	NM_001040663.4	c.*160C>A		3_prime_UTR_variant	5/5	ENST00000381700.11	NP_001035753.1
GAGE1	NR_102272.2	n.780C>A		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAGE1	ENST00000381700.11	c.*160C>A		3_prime_UTR_variant	5/5	1	NM_001040663.4	ENSP00000371119	P1
GAGE1	ENST00000381709.6	c.*237C>A		3_prime_UTR_variant, NMD_transcript_variant	6/6	2		ENSP00000371128

Frequencies

GnomAD3 genomes AF: 0.440 AC: 48173 AN: 109388 Hom.: 9041 Cov.: 22 AF XY: 0.427 AC XY: 13604 AN XY: 31836

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.472

GnomAD4 exome AF: 0.560 AC: 105301 AN: 188044 Hom.: 21774 Cov.: 4 AF XY: 0.604 AC XY: 28907 AN XY: 47882

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.626

Gnomad4 EAS exome AF: 0.407

Gnomad4 SAS exome AF: 0.634

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.612

Gnomad4 OTH exome AF: 0.543

GnomAD4 genome AF: 0.440 AC: 48174 AN: 109419 Hom.: 9041 Cov.: 22 AF XY: 0.427 AC XY: 13615 AN XY: 31879

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.477

Alfa AF: 0.450 Hom.: 4998

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.32
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5906843; hg19: chrX-49370778; COSMIC: COSV67748002; COSMIC: COSV67748002;