rs17501837

Positions:

chr2-215037050-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.189

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein
ABCA12	NM_173076.3 linkuse as main transcript	c.888G>A	p.Val296=	synonymous_variant	8/53	ENST00000272895.12	NP_775099.2
ABCA12	XM_011510951.3 linkuse as main transcript	c.888G>A	p.Val296=	synonymous_variant	8/53		XP_011509253.1
ABCA12	NR_103740.2 linkuse as main transcript	n.1330G>A		non_coding_transcript_exon_variant	9/55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12 linkuse as main transcript	c.888G>A	p.Val296=	synonymous_variant	8/53	1	NM_173076.3	ENSP00000272895	P1	Q86UK0-1
	ENST00000628464.2 linkuse as main transcript	n.716+1217C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29031

AN:

151974

Hom.:

3001

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.206

AC XY:

149795

AN XY:

726594

show subpopulations

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.:

AF XY:

0.190

AC XY:

14093

AN XY:

74358

show subpopulations

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over