rs12304921

Variant names:

• chr12-50963759-A-G
• rs12304921
• NM_001109619.4:c.229+2657A>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]

ENSG00000289695 (HGNC:):

SLC11A2 (HGNC:10908): (solute carrier family 11 member 2) This gene encodes a member of the solute carrier family 11 protein family. The product of this gene transports divalent metals and is involved in iron absorption. Mutations in this gene are associated with hypochromic microcytic anemia with iron overload. A related solute carrier family 11 protein gene is located on chromosome 2. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2010]

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 rank	MANE	Protein	UniProt
HIGD1C	NM_001109619.4	c.229+2657A>G		intron_variant	Intron 4 of 4	ENST00000695931.1	NP_001103089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIGD1C	ENST00000695931.1	c.229+2657A>G		intron_variant	Intron 4 of 4		NM_001109619.4	ENSP00000512274.1
HIGD1C	ENST00000398455.3	c.229+2657A>G		intron_variant	Intron 2 of 2	1		ENSP00000381473.3
ENSG00000289695	ENST00000695929.1	n.*534+2657A>G		intron_variant	Intron 6 of 6			ENSP00000512272.1
HIGD1C	ENST00000695930.1	c.253+2657A>G		intron_variant	Intron 3 of 3			ENSP00000512273.1

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;