dbSNP rs7178130: HIGD2B:c.-236C>T (chr15-72685861-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 NM_001350932.3(HIGD2B):c.-236C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 371,740 control chromosomes in the GnomAD database, including 62,861 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 0.53 ( 22979 hom., cov: 32)

Exomes 𝑓: 0.59 ( 39882 hom. )

Consequence

HIGD2B
NM_001350932.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.234

Publications

17 publications found

Variant links:

Genes affected

HIGD2B (HGNC:26984): (HIG1 hypoxia inducible domain family member 2B) Predicted to be involved in mitochondrial respirasome assembly. Predicted to be integral component of membrane. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

HIGD2B 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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350932.3. 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
	HIGD2B	NM_001350932.3	MANE Select	c.-236C>T		5_prime_UTR	Exon 1 of 3	NP_001337861.1	Q4VC39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIGD2B	ENST00000311755.6	TSL:1 MANE Select	c.-236C>T		5_prime_UTR	Exon 1 of 3	ENSP00000307951.3	Q4VC39
	HIGD2B	ENST00000911655.1		c.-336C>T		5_prime_UTR	Exon 1 of 4	ENSP00000581714.1

Frequencies

GnomAD3 genomes

AF:

0.527

AC:

80068

AN:

151924

Hom.:

22998

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.696

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.578

Gnomad FIN

AF:

0.655

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.637

Gnomad OTH

AF:

0.554

GnomAD4 exome

AF:

0.587

AC:

129055

AN:

219696

Hom.:

39882

Cov.:

AF XY:

0.589

AC XY:

68419

AN XY:

116118

show subpopulations

African (AFR)

AF:

0.323

AC:

2337

AN:

7240

American (AMR)

AF:

0.503

AC:

4719

AN:

9374

Ashkenazi Jewish (ASJ)

AF:

0.670

AC:

4245

AN:

6332

East Asian (EAS)

AF:

0.208

AC:

2505

AN:

12064

South Asian (SAS)

AF:

0.591

AC:

18878

AN:

31960

European-Finnish (FIN)

AF:

0.652

AC:

7587

AN:

11630

Middle Eastern (MID)

AF:

0.655

AC:

584

AN:

892

European-Non Finnish (NFE)

AF:

0.634

AC:

81079

AN:

127962

Other (OTH)

AF:

0.582

AC:

7121

AN:

12242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

2340

4680

7019

9359

11699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.527

AC:

80063

AN:

152044

Hom.:

22979

Cov.:

AF XY:

0.530

AC XY:

39366

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.325

AC:

13475

AN:

41400

American (AMR)

AF:

0.529

AC:

8087

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.672

AC:

2334

AN:

3472

East Asian (EAS)

AF:

0.225

AC:

1164

AN:

5178

South Asian (SAS)

AF:

0.577

AC:

2784

AN:

4822

European-Finnish (FIN)

AF:

0.655

AC:

6927

AN:

10582

Middle Eastern (MID)

AF:

0.673

AC:

198

AN:

294

European-Non Finnish (NFE)

AF:

0.637

AC:

43302

AN:

67988

Other (OTH)

AF:

0.548

AC:

1157

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1779

3558

5338

7117

8896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.580

Hom.:

39215

Bravo

AF:

0.508

Asia WGS

AF:

0.384

AC:

1340

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.8

(source)

DANN

Benign

0.85

PhyloP100

-0.23

PromoterAI

-0.034

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over