ENST00000376800.7:n.179G>A

Variant names:

• chr6-29975290-G-A
• rs6904029
• ENST00000376800.7:n.179G>A

Variant summary

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

The ENST00000376800.7(HCG9):​n.179G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 528,338 control chromosomes in the GnomAD database, including 21,577 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 0.26 (5502 hom., cov: 30)
  • Exomes 𝑓: 0.28 (16075 hom.)
• Consequence: HCG9 ENST00000376800.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.655
• Publications: 54 publications found

Genes affected

HCG9 (HGNC:21243): (HLA complex group 9) This gene lies within the MHC class I region on chromosome 6p21.3. This gene is believed to be non-coding, but its function has not been determined. [provided by RefSeq, Jul 2009]

MICD (HGNC:7093): (MHC class I polypeptide-related sequence D (pseudogene))

POLR1HASP (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCG9	NR_028032.1	n.176G>A		non_coding_transcript_exon_variant	Exon 1 of 3
MICD		n.29975290G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCG9	ENST00000376800.7	n.179G>A		non_coding_transcript_exon_variant	Exon 1 of 3	1
POLR1HASP	ENST00000849678.1	n.589-28374C>T		intron_variant	Intron 3 of 4
POLR1HASP	ENST00000849679.1	n.65+1313C>T		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39696 AN: 151628 Hom.: 5502 Cov.: 30

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.240

GnomAD2 exomes AF: 0.291 AC: 67287 AN: 231422 AF XY: 0.284

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.330

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.329

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.310

Gnomad OTH exome AF: 0.272

GnomAD4 exome AF: 0.283 AC: 106465 AN: 376592 Hom.: 16075 Cov.: 0 AF XY: 0.272 AC XY: 58234 AN XY: 214172

African (AFR) AF: 0.200 AC: 2099 AN: 10492

American (AMR) AF: 0.326 AC: 11328 AN: 34774

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 2245 AN: 11628

East Asian (EAS) AF: 0.322 AC: 4296 AN: 13340

South Asian (SAS) AF: 0.176 AC: 11563 AN: 65552

European-Finnish (FIN) AF: 0.366 AC: 11386 AN: 31140

Middle Eastern (MID) AF: 0.255 AC: 725 AN: 2846

European-Non Finnish (NFE) AF: 0.306 AC: 58237 AN: 190232

Other (OTH) AF: 0.276 AC: 4586 AN: 16588

GnomAD4 genome AF: 0.262 AC: 39692 AN: 151746 Hom.: 5502 Cov.: 30 AF XY: 0.261 AC XY: 19354 AN XY: 74112

African (AFR) AF: 0.199 AC: 8242 AN: 41380

American (AMR) AF: 0.250 AC: 3824 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3466

East Asian (EAS) AF: 0.311 AC: 1588 AN: 5100

South Asian (SAS) AF: 0.169 AC: 815 AN: 4814

European-Finnish (FIN) AF: 0.360 AC: 3794 AN: 10530

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19959 AN: 67868

Other (OTH) AF: 0.237 AC: 500 AN: 2112

Alfa AF: 0.277 Hom.: 17705

Bravo AF: 0.255

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.73
PhyloP100		0.66

Splicing

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

Other links and lift over

dbSNP: rs6904029; hg19: chr6-29943067; COSMIC: COSV65136300;