2-214932608-C-T

Position:

chr2-214932608-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173076.3(ABCA12):c.*26G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,524,524 control chromosomes in the GnomAD database, including 128,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12214 hom., cov: 32)

Exomes 𝑓: 0.41 ( 116741 hom. )

Consequence

ABCA12
NM_173076.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.787

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:

SNHG31 (HGNC:54196): (small nucleolar RNA host gene 31)

SNHG31 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 (BayesDel_noAF=-0.96).

BP6

Variant 2-214932608-C-T is Benign according to our data. Variant chr2-214932608-C-T is described in ClinVar as [Benign]. Clinvar id is 334218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-214932608-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA12	NM_173076.3 link	c.*26G>A		3_prime_UTR_variant	53/53	ENST00000272895.12	NP_775099.2	Q86UK0-1B3KVV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895 link	c.*26G>A		3_prime_UTR_variant	53/53	1	NM_173076.3	ENSP00000272895.7		Q86UK0-1

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60741

AN:

151852

Hom.:

12209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.460

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.411

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.410

Gnomad OTH

AF:

0.390

GnomAD3 exomes

AF:

0.421

AC:

104291

AN:

247654

Hom.:

22232

AF XY:

0.427

AC XY:

57160

AN XY:

133830

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.440

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.522

Gnomad FIN exome

AF:

0.425

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.403

GnomAD4 exome

AF:

0.409

AC:

561683

AN:

1372554

Hom.:

116741

Cov.:

AF XY:

0.413

AC XY:

284359

AN XY:

687962

show subpopulations

Gnomad4 AFR exome

AF:

0.348

Gnomad4 AMR exome

AF:

0.437

Gnomad4 ASJ exome

AF:

0.449

Gnomad4 EAS exome

AF:

0.364

Gnomad4 SAS exome

AF:

0.526

Gnomad4 FIN exome

AF:

0.432

Gnomad4 NFE exome

AF:

0.400

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.400

AC:

60783

AN:

151970

Hom.:

12214

Cov.:

AF XY:

0.405

AC XY:

30048

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.432

Gnomad4 ASJ

AF:

0.460

Gnomad4 EAS

AF:

0.356

Gnomad4 SAS

AF:

0.526

Gnomad4 FIN

AF:

0.411

Gnomad4 NFE

AF:

0.410

Gnomad4 OTH

AF:

0.389

Alfa

AF:

0.405

Hom.:

3286

Bravo

AF:

0.392

Asia WGS

AF:

0.405

AC:

1410

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Autosomal recessive congenital ichthyosis 4A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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. -

Autosomal recessive congenital ichthyosis 4B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.36

DANN

Benign

0.68

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