rs10498030

Variant names:

• chr2-215000851-T-C
• rs10498030
• NM_173076.3:c.3033A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-215000851-T-C
• chr2-215000851-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_173076.3(ABCA12):​c.3033A>G​(p.Pro1011Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,613,940 control chromosomes in the GnomAD database, including 49,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3918 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46073 hom.)
• Consequence: ABCA12 NM_173076.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.26
• Publications: 19 publications found

Genes affected

ABCA12 (HGNC:14637): (ATP binding cassette subfamily A member 12) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This encoded protein is a member of the ABC1 subfamily, which is the only major ABC subfamily found exclusively in multicellular eukaryotes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ABCA12 Gene-Disease associations (from GenCC):

• autosomal recessive congenital ichthyosis 4B

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, PanelApp Australia, Orphanet, G2P
• autosomal recessive congenital ichthyosis 4A

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital non-bullous ichthyosiform erythroderma

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 2-215000851-T-C is Benign according to our data. Variant chr2-215000851-T-C is described in ClinVar as Benign. ClinVar VariationId is 262825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA12	NM_173076.3	c.3033A>G	p.Pro1011Pro	synonymous_variant	Exon 22 of 53	ENST00000272895.12	NP_775099.2
ABCA12	NM_015657.4	c.2079A>G	p.Pro693Pro	synonymous_variant	Exon 14 of 45		NP_056472.2
ABCA12	XM_011510951.3	c.3033A>G	p.Pro1011Pro	synonymous_variant	Exon 22 of 53		XP_011509253.1
ABCA12	NR_103740.2	n.3475A>G		non_coding_transcript_exon_variant	Exon 23 of 55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12	c.3033A>G	p.Pro1011Pro	synonymous_variant	Exon 22 of 53	1	NM_173076.3	ENSP00000272895.7
ABCA12	ENST00000389661.4	c.2079A>G	p.Pro693Pro	synonymous_variant	Exon 14 of 45	1		ENSP00000374312.4

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30538 AN: 152004 Hom.: 3918 Cov.: 32

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.217

GnomAD2 exomes AF: 0.235 AC: 59159 AN: 251374 AF XY: 0.238

Gnomad AFR exome AF: 0.0399

Gnomad AMR exome AF: 0.166

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.374

Gnomad FIN exome AF: 0.348

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.246 AC: 359087 AN: 1461818 Hom.: 46073 Cov.: 37 AF XY: 0.245 AC XY: 177997 AN XY: 727214

African (AFR) AF: 0.0356 AC: 1191 AN: 33478

American (AMR) AF: 0.167 AC: 7467 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 5304 AN: 26132

East Asian (EAS) AF: 0.344 AC: 13648 AN: 39698

South Asian (SAS) AF: 0.179 AC: 15442 AN: 86256

European-Finnish (FIN) AF: 0.339 AC: 18126 AN: 53416

Middle Eastern (MID) AF: 0.219 AC: 1263 AN: 5768

European-Non Finnish (NFE) AF: 0.254 AC: 282276 AN: 1111960

Other (OTH) AF: 0.238 AC: 14370 AN: 60394

GnomAD4 genome AF: 0.201 AC: 30519 AN: 152122 Hom.: 3918 Cov.: 32 AF XY: 0.206 AC XY: 15292 AN XY: 74346

African (AFR) AF: 0.0454 AC: 1884 AN: 41542

American (AMR) AF: 0.187 AC: 2851 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3470

East Asian (EAS) AF: 0.359 AC: 1852 AN: 5164

South Asian (SAS) AF: 0.186 AC: 894 AN: 4814

European-Finnish (FIN) AF: 0.359 AC: 3793 AN: 10574

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17673 AN: 67972

Other (OTH) AF: 0.215 AC: 454 AN: 2108

Alfa AF: 0.234 Hom.: 8837

Bravo AF: 0.185

Asia WGS AF: 0.228 AC: 793 AN: 3478

EpiCase AF: 0.259

EpiControl AF: 0.263

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive congenital ichthyosis 4A Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital ichthyosis of skin Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal recessive congenital ichthyosis 4B Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.7
DANN	Benign	0.76
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10498030; hg19: chr2-215865575; COSMIC: COSV55971556; COSMIC: COSV55971556;