6-31057274-T-C

Variant names:

• chr6-31057274-T-C
• rs2523849
• ENST00000426185.2:n.1559+364T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000426185.2(HCG22):​n.1559+364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,888 control chromosomes in the GnomAD database, including 3,736 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 0.21 (3736 hom., cov: 31)
• Consequence: HCG22 ENST00000426185.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 28 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000426185.2. 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
	HCG22	NR_003948.3		n.1701+364T>C		intron	N/A
	HCG22	NR_145427.2		n.1193+364T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCG22	ENST00000426185.2	TSL:2	n.1559+364T>C		intron	N/A
	HCG22	ENST00000562344.2	TSL:5	n.1287+364T>C		intron	N/A
	HCG22	ENST00000565192.1	TSL:2	n.1192+364T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32002 AN: 151770 Hom.: 3728 Cov.: 31

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.211 AC: 32038 AN: 151888 Hom.: 3736 Cov.: 31 AF XY: 0.214 AC XY: 15876 AN XY: 74258

African (AFR) AF: 0.276 AC: 11443 AN: 41396

American (AMR) AF: 0.214 AC: 3272 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1516 AN: 3462

East Asian (EAS) AF: 0.282 AC: 1458 AN: 5168

South Asian (SAS) AF: 0.366 AC: 1759 AN: 4804

European-Finnish (FIN) AF: 0.136 AC: 1437 AN: 10550

Middle Eastern (MID) AF: 0.262 AC: 76 AN: 290

European-Non Finnish (NFE) AF: 0.154 AC: 10476 AN: 67918

Other (OTH) AF: 0.245 AC: 519 AN: 2116

Alfa AF: 0.192 Hom.: 7576

Bravo AF: 0.215

Asia WGS AF: 0.338 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.4
DANN	Benign	0.35
PhyloP100		0.19

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2523849;

hg19: chr6-31025051;