rs240444

Variant names:

• chr21-10510446-A-G
• rs240444
• ENST00000496773.1:n.2356-3676A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000496773.1(BAGE2):​n.2356-3676A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 142,858 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.14 (0 hom., cov: 34)
• Consequence: BAGE2 ENST00000496773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 3 publications found

Genes affected

BAGE2 (HGNC:15723): (BAGE family member 2 (pseudogene)) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000273840 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Variant has high frequency in the NFE (0.146) population. However there is too low homozygotes in high coverage region: (expected more than 741, got 0).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAGE2	NR_169269.1	n.2115-3676A>G		intron_variant	Intron 11 of 12
BAGE2	NR_169270.1	n.1836-3676A>G		intron_variant	Intron 9 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAGE2	ENST00000496773.1	n.2356-3676A>G		intron_variant	Intron 13 of 14	6
ENSG00000273840	ENST00000612267.1	n.1218-3676A>G		intron_variant	Intron 9 of 31	5
ENSG00000273840	ENST00000807378.1	n.551-3676A>G		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 20577 AN: 142734 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0826

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.144 AC: 20578 AN: 142858 Hom.: 0 Cov.: 34 AF XY: 0.145 AC XY: 10118 AN XY: 69784

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.138 AC: 5336 AN: 38736

American (AMR) AF: 0.119 AC: 1719 AN: 14390

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 487 AN: 3238

East Asian (EAS) AF: 0.0830 AC: 410 AN: 4940

South Asian (SAS) AF: 0.136 AC: 611 AN: 4496

European-Finnish (FIN) AF: 0.204 AC: 1996 AN: 9782

Middle Eastern (MID) AF: 0.177 AC: 50 AN: 282

European-Non Finnish (NFE) AF: 0.148 AC: 9515 AN: 64154

Other (OTH) AF: 0.149 AC: 297 AN: 1998

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.157 Hom.: 53

Asia WGS AF: 0.135 AC: 472 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.6
DANN	Benign	0.58
PhyloP100		0.076

Splicing

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

Other links and lift over

dbSNP: rs240444; hg19: chr21-11002011;