ENST00000453558.2:n.663-2172G>C

Variant names:

• chr6-30236622-C-G
• rs2523742
• ENST00000453558.2:n.663-2172G>C

Variant summary

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

The ENST00000453558.2(HCG18):​n.663-2172G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,162 control chromosomes in the GnomAD database, including 1,000 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 0.10 (1000 hom., cov: 32)
• Consequence: HCG18 ENST00000453558.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 16 publications found

Genes affected

HCG18 (HGNC:31337): (HLA complex group 18)

HCG17 (HGNC:31339): (HLA complex group 17)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000453558.2. 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
	HCG17	NR_052012.1		n.410-2172G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCG18	ENST00000453558.2	TSL:5	n.663-2172G>C		intron	N/A
	HCG18	ENST00000844410.1		n.317-2172G>C		intron	N/A
	HCG18	ENST00000844411.1		n.361-2172G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15815 AN: 152044 Hom.: 993 Cov.: 32

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.0668

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0876

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.0893

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

GnomAD4 genome AF: 0.104 AC: 15851 AN: 152162 Hom.: 1000 Cov.: 32 AF XY: 0.0988 AC XY: 7349 AN XY: 74390

African (AFR) AF: 0.0898 AC: 3728 AN: 41500

American (AMR) AF: 0.0642 AC: 980 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0668 AC: 232 AN: 3472

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5178

South Asian (SAS) AF: 0.0601 AC: 290 AN: 4828

European-Finnish (FIN) AF: 0.0876 AC: 927 AN: 10584

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9294 AN: 68002

Other (OTH) AF: 0.0950 AC: 201 AN: 2116

Alfa AF: 0.121 Hom.: 150

Bravo AF: 0.101

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.3
DANN	Benign	0.93
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism

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: rs2523742;

hg19: chr6-30204399;