Genetic Variant ENST00000376800.7:n.381G>A (chr6-29975492-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000376800.7(HCG9):n.381G>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 0.194 in 381,338 control chromosomes in the GnomAD database, including 8,199 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 0.22 ( 4154 hom., cov: 30)

Exomes 𝑓: 0.18 ( 4045 hom. )

Consequence

HCG9
ENST00000376800.7 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.566

Publications

12 publications found

Variant links:

COSMIC-nc: COSV65136142

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]

HCG9 links:

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

MICD links:

POLR1HASP (HGNC:):

POLR1HASP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCG9	NR_028032.1 link	n.378G>A		non_coding_transcript_exon_variant	Exon 1 of 3
MICD		n.29975492G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
HCG9	ENST00000376800.7 link	n.381G>A	non_coding_transcript_exon_variant	Exon 1 of 3	1
POLR1HASP	ENST00000849678.1 link	n.589-28576C>T	intron_variant	Intron 3 of 4
POLR1HASP	ENST00000849679.1 link	n.65+1111C>T	intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33188

AN:

151724

Hom.:

4136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.241

GnomAD4 exome

AF:

0.178

AC:

40800

AN:

229496

Hom.:

4045

Cov.:

AF XY:

0.184

AC XY:

23308

AN XY:

126882

show subpopulations

African (AFR)

AF:

0.324

AC:

1758

AN:

5432

American (AMR)

AF:

0.277

AC:

3391

AN:

12220

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

915

AN:

4836

East Asian (EAS)

AF:

0.164

AC:

1396

AN:

8508

South Asian (SAS)

AF:

0.233

AC:

10363

AN:

44496

European-Finnish (FIN)

AF:

0.131

AC:

3151

AN:

24020

Middle Eastern (MID)

AF:

0.199

AC:

156

AN:

784

European-Non Finnish (NFE)

AF:

0.150

AC:

17887

AN:

118918

Other (OTH)

AF:

0.173

AC:

1783

AN:

10282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

1487

2973

4460

5946

7433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

384

576

768

960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.219

AC:

33257

AN:

151842

Hom.:

4154

Cov.:

AF XY:

0.217

AC XY:

16136

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.330

AC:

13647

AN:

41308

American (AMR)

AF:

0.277

AC:

4230

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

670

AN:

3470

East Asian (EAS)

AF:

0.139

AC:

719

AN:

5160

South Asian (SAS)

AF:

0.238

AC:

1145

AN:

4806

European-Finnish (FIN)

AF:

0.126

AC:

1329

AN:

10580

Middle Eastern (MID)

AF:

0.223

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.160

AC:

10845

AN:

67940

Other (OTH)

AF:

0.238

AC:

503

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1141

2282

3422

4563

5704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.232

Hom.:

1141

Bravo

AF:

0.238

Asia WGS

AF:

0.186

AC:

644

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.0

(source)

DANN

Benign

0.76

PhyloP100

-0.57

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over