6-31062447-C-T

Variant names:

• chr6-31062447-C-T
• rs2517509
• ENST00000805383.1:n.734-1562C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000805383.1(HCG22):​n.734-1562C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 152,188 control chromosomes in the GnomAD database, including 68 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 0.022 (68 hom., cov: 32)
• Consequence: HCG22 ENST00000805383.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 15 publications found

Genes affected

HCG22 (HGNC:27780): (HLA complex group 22 (non-protein coding)) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0224 (3404/152188) while in subpopulation AMR AF = 0.0396 (605/15272). AF 95% confidence interval is 0.037. There are 68 homozygotes in GnomAd4. There are 1550 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 68 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCG22	ENST00000805383.1	n.734-1562C>T		intron_variant	Intron 2 of 2
HCG22	ENST00000805384.1	n.554-1562C>T		intron_variant	Intron 2 of 2
HCG22	ENST00000805385.1	n.460-1562C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3404 AN: 152070 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0396

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.0359

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

GnomAD4 genome AF: 0.0224 AC: 3404 AN: 152188 Hom.: 68 Cov.: 32 AF XY: 0.0208 AC XY: 1550 AN XY: 74402

African (AFR) AF: 0.0286 AC: 1187 AN: 41520

American (AMR) AF: 0.0396 AC: 605 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 380 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00229 AC: 11 AN: 4814

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10596

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0165 AC: 1123 AN: 68014

Other (OTH) AF: 0.0355 AC: 75 AN: 2112

Alfa AF: 0.0199 Hom.: 114

Bravo AF: 0.0269

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		0.074

Splicing

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

Other links and lift over

dbSNP: rs2517509; hg19: chr6-31030224;