rs12304921

chr12-50963759-A-G

Variant summary

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

The NM_001109619.4(HIGD1C):c.229+2657A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,184 control chromosomes in the GnomAD database, including 2,918 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 0.18 (2918 hom., cov: 32)
• Consequence: HIGD1C NM_001109619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

Genes affected

HIGD1C (HGNC:28044): (HIG1 hypoxia inducible domain family member 1C) 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]

SLC11A2 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIGD1C	NM_001109619.4	c.229+2657A>G		intron_variant		ENST00000695931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIGD1C	ENST00000695931.1	c.229+2657A>G		intron_variant			NM_001109619.4	P1
HIGD1C	ENST00000398455.3	c.229+2657A>G		intron_variant		1		P1
HIGD1C	ENST00000695930.1	c.253+2657A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27806 AN: 152066 Hom.: 2910 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.183 AC: 27846 AN: 152184 Hom.: 2918 Cov.: 32 AF XY: 0.189 AC XY: 14034 AN XY: 74406

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.174

Alfa AF: 0.173 Hom.: 3601

Bravo AF: 0.180

Asia WGS AF: 0.362 AC: 1264 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	6.4
Dann	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs12304921; hg19: chr12-51357542;