rs261946

chr6-30303557-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_024053.2(HCG18):n.804-7320T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,186 control chromosomes in the GnomAD database, including 3,626 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 0.20 (3626 hom., cov: 31)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: HCG18 NR_024053.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

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

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCG18	NR_024053.2	n.804-7320T>C		intron_variant, non_coding_transcript_variant
HCG17	NR_052012.1	n.126+22452T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCG17	ENST00000453558.1	n.126+22452T>C		intron_variant, non_coding_transcript_variant		5
HCG18	ENST00000670397.1	n.143-7320T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29758 AN: 152062 Hom.: 3625 Cov.: 31

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.196 AC: 29770 AN: 152180 Hom.: 3626 Cov.: 31 AF XY: 0.199 AC XY: 14781 AN XY: 74388

Gnomad4 AFR AF: 0.0573

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.154

Alfa AF: 0.235 Hom.: 4648

Bravo AF: 0.179

Asia WGS AF: 0.152 AC: 528 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	3.2
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs261946; hg19: chr6-30271334;