dbSNP rs12304921: HIGD1C:c.229+2657A>G (chr12-50963759-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0910

Publications

34 publications found

Variant links:

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]

HIGD1C links:

ENSG00000289695 (HGNC:):

ENSG00000289695 links:

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]

SLC11A2 Gene-Disease associations (from GenCC):

microcytic anemia with liver iron overload
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics, Genomics England PanelApp

SLC11A2 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 (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109619.4. 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
	HIGD1C	NM_001109619.4	MANE Select	c.229+2657A>G		intron	N/A	NP_001103089.1	A8MV81

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HIGD1C	ENST00000695931.1	MANE Select	c.229+2657A>G	intron	N/A	ENSP00000512274.1	A8MV81
HIGD1C	ENST00000398455.3	TSL:1	c.229+2657A>G	intron	N/A	ENSP00000381473.3	A8MV81
ENSG00000289695	ENST00000695929.1		n.*534+2657A>G	intron	N/A	ENSP00000512272.1	A0A8Q3SIA8

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27806

AN:

152066

Hom.:

2910

Cov.:

show subpopulations

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.:

AF XY:

0.189

AC XY:

14034

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.173

AC:

7202

AN:

41516

American (AMR)

AF:

0.165

AC:

2523

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

704

AN:

3468

East Asian (EAS)

AF:

0.499

AC:

2575

AN:

5164

South Asian (SAS)

AF:

0.288

AC:

1388

AN:

4824

European-Finnish (FIN)

AF:

0.188

AC:

1991

AN:

10596

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.158

AC:

10717

AN:

68002

Other (OTH)

AF:

0.174

AC:

368

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1125

2250

3375

4500

5625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.173

Hom.:

5999

Bravo

AF:

0.180

Asia WGS

AF:

0.362

AC:

1264

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

6.4

(source)

DANN

Benign

0.91

PhyloP100

0.091

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over