rs7178130

Positions:

• chr15-72685861-G-A
• chr15-72685861-G-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIGD2B	NM_001350932.3	c.-236C>T		5_prime_UTR_variant	1/3	ENST00000311755.6	NP_001337861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIGD2B	ENST00000311755.6	c.-236C>T		5_prime_UTR_variant	1/3	1	NM_001350932.3	ENSP00000307951	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80068 AN: 151924 Hom.: 22998 Cov.: 32

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.: 0 AF XY: 0.589 AC XY: 68419 AN XY: 116118

Gnomad4 AFR exome AF: 0.323

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.670

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.591

Gnomad4 FIN exome AF: 0.652

Gnomad4 NFE exome AF: 0.634

Gnomad4 OTH exome AF: 0.582

GnomAD4 genome AF: 0.527 AC: 80063 AN: 152044 Hom.: 22979 Cov.: 32 AF XY: 0.530 AC XY: 39366 AN XY: 74328

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.548

Alfa AF: 0.507 Hom.: 3176

Bravo AF: 0.508

Asia WGS AF: 0.384 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.85

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

LitVar

Other links and lift over

dbSNP: rs7178130; hg19: chr15-72978202; COSMIC: COSV51440585; COSMIC: COSV51440585;