rs17501837

chr2-215037050-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_173076.3(ABCA12):c.888G>A(p.Val296=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,612,510 control chromosomes in the GnomAD database, including 37,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2995 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34288 hom.)
• Consequence: ABCA12 NM_173076.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.189

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-215037050-C-T is Benign according to our data. Variant chr2-215037050-C-T is described in ClinVar as [Benign]. Clinvar id is 262834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215037050-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.189 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA12	NM_173076.3	c.888G>A	p.Val296=	synonymous_variant	8/53	ENST00000272895.12
ABCA12	XM_011510951.3	c.888G>A	p.Val296=	synonymous_variant	8/53
ABCA12	NR_103740.2	n.1330G>A		non_coding_transcript_exon_variant	9/55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA12	ENST00000272895.12	c.888G>A	p.Val296=	synonymous_variant	8/53	1	NM_173076.3	P1
	ENST00000628464.2	n.716+1217C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29031 AN: 151974 Hom.: 3001 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.204

GnomAD3 exomes AF: 0.212 AC: 53177 AN: 251314 Hom.: 6360 AF XY: 0.205 AC XY: 27856 AN XY: 135842

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.395

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.206

GnomAD4 exome AF: 0.209 AC: 305910 AN: 1460418 Hom.: 34288 Cov.: 32 AF XY: 0.206 AC XY: 149795 AN XY: 726594

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.191 AC: 29029 AN: 152092 Hom.: 2995 Cov.: 32 AF XY: 0.190 AC XY: 14093 AN XY: 74358

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.204

Alfa AF: 0.203 Hom.: 6348

Bravo AF: 0.198

Asia WGS AF: 0.277 AC: 963 AN: 3478

EpiCase AF: 0.199

EpiControl AF: 0.201

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Congenital ichthyosis of skin Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	4.6
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17501837; hg19: chr2-215901774; COSMIC: COSV55952938; COSMIC: COSV55952938;