chrX-49606175-C-A

Variant names:

• chrX-49606175-C-A
• rs5906843
• NM_001040663.4:c.*160C>A

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GAGE1	NM_001040663.4	c.*160C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000381700.11	NP_001035753.1
GAGE1	NR_102272.2	n.780C>A		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAGE1	ENST00000381700.11	c.*160C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_001040663.4	ENSP00000371119.5
GAGE1	ENST00000381709.6	n.*237C>A		non_coding_transcript_exon_variant	Exon 6 of 6	2		ENSP00000371128.2
GAGE1	ENST00000381709.6	n.*237C>A		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000371128.2

Frequencies

GnomAD3 genomes AF: 0.440 AC: 48173 AN: 109388 Hom.: 9041 Cov.: 22

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 AC: 935 AN: 5362

Gnomad4 AMR exome AF: 0.419 AC: 3274 AN: 7822

Gnomad4 ASJ exome AF: 0.626 AC: 3029 AN: 4838

Gnomad4 EAS exome AF: 0.407 AC: 6171 AN: 15160

Gnomad4 SAS exome AF: 0.634 AC: 2654 AN: 4184

Gnomad4 FIN exome AF: 0.515 AC: 12084 AN: 23470

Gnomad4 NFE exome AF: 0.612 AC: 71140 AN: 116242

Gnomad4 Remaining exome AF: 0.543 AC: 5617 AN: 10336

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 AC: 0.16338 AN: 0.16338

Gnomad4 AMR AF: 0.422 AC: 0.421903 AN: 0.421903

Gnomad4 ASJ AF: 0.609 AC: 0.608613 AN: 0.608613

Gnomad4 EAS AF: 0.378 AC: 0.3779 AN: 0.3779

Gnomad4 SAS AF: 0.562 AC: 0.562233 AN: 0.562233

Gnomad4 FIN AF: 0.480 AC: 0.479978 AN: 0.479978

Gnomad4 NFE AF: 0.588 AC: 0.587795 AN: 0.587795

Gnomad4 OTH AF: 0.477 AC: 0.476861 AN: 0.476861

Alfa AF: 0.467 Hom.: 6710

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
Mutation Taster		=100/0	polymorphism (auto)

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;