rs76979001

Positions:

chr2-215015554-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_173076.3(ABCA12):c.1892G>A(p.Arg631Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,614,026 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 42 hom. )

Consequence

ABCA12
NM_173076.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.519

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:

ABCA12 (HGNC:):

ABCA12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032784045).

BP6

Variant 2-215015554-C-T is Benign according to our data. Variant chr2-215015554-C-T is described in ClinVar as [Benign]. Clinvar id is 262822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00274 (417/152224) while in subpopulation AMR AF= 0.0153 (234/15294). AF 95% confidence interval is 0.0137. There are 3 homozygotes in gnomad4. There are 235 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA12	NM_173076.3 linkuse as main transcript	c.1892G>A	p.Arg631Gln	missense_variant	15/53	ENST00000272895.12	NP_775099.2	Q86UK0-1B3KVV3
ABCA12	NM_015657.4 linkuse as main transcript	c.938G>A	p.Arg313Gln	missense_variant	7/45		NP_056472.2	Q86UK0-2B3KVV3
ABCA12	XM_011510951.3 linkuse as main transcript	c.1892G>A	p.Arg631Gln	missense_variant	15/53		XP_011509253.1
ABCA12	NR_103740.2 linkuse as main transcript	n.2334G>A		non_coding_transcript_exon_variant	16/55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCA12	ENST00000272895.12 linkuse as main transcript	c.1892G>A	p.Arg631Gln	missense_variant	15/53	1	NM_173076.3	ENSP00000272895.7	Q86UK0-1
ABCA12	ENST00000389661.4 linkuse as main transcript	c.938G>A	p.Arg313Gln	missense_variant	7/45	1		ENSP00000374312.4	Q86UK0-2
ENSG00000227769	ENST00000617699.1 linkuse as main transcript	n.191-2108C>T		intron_variant		5
ENSG00000227769	ENST00000627811.1 linkuse as main transcript	n.73+2337C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00272

AC:

413

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0120

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00774

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00669

AC:

1682

AN:

251296

Hom.:

AF XY:

0.00540

AC XY:

734

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0383

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0116

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00448

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00174

AC:

2540

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1169

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.0359

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0137

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00384

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00274

AC:

417

AN:

152224

Hom.:

Cov.:

AF XY:

0.00316

AC XY:

235

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.0153

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0122

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00774

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000761

Hom.:

Bravo

AF:

0.00479

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00525

AC:

637

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Benign

8.4

DANN

Benign

0.95

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.5

L;.

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.66

N;N

REVEL

Benign

0.14

Sift

Benign

0.20

T;T

Sift4G

Uncertain

0.024

D;T

Polyphen

0.41

B;B

Vest4

0.23

MVP

0.66

MPC

0.26

ClinPred

0.0024

GERP RS

2.4

Varity_R

0.024

gMVP

0.34

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

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