rs2274412

Variant summary

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

The NM_173076.3(ABCA12):c.7105-17C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 1,612,098 control chromosomes in the GnomAD database, including 165,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21622 hom., cov: 31)

Exomes 𝑓: 0.44 ( 144333 hom. )

Consequence

ABCA12
NM_173076.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.40

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=-0.78).

BP6

Variant 2-214947573-G-A is Benign according to our data. Variant chr2-214947573-G-A is described in ClinVar as [Benign]. Clinvar id is 262833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-214947573-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA12	NM_173076.3 linkuse as main transcript	c.7105-17C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000272895.12
SNHG31	NR_110292.1 linkuse as main transcript	n.322-252G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA12	ENST00000272895.12 linkuse as main transcript	c.7105-17C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_173076.3	P1	Q86UK0-1
SNHG31	ENST00000670391.1 linkuse as main transcript	n.438-14237G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78738

AN:

151700

Hom.:

21600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.599

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.492

Gnomad EAS

AF:

0.355

Gnomad SAS

AF:

0.521

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.509

GnomAD3 exomes

AF:

0.463

AC:

115703

AN:

249900

Hom.:

27669

AF XY:

0.461

AC XY:

62257

AN XY:

135018

show subpopulations

Gnomad AFR exome

AF:

0.718

Gnomad AMR exome

AF:

0.481

Gnomad ASJ exome

AF:

0.493

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.519

Gnomad FIN exome

AF:

0.428

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.440

AC:

643240

AN:

1460280

Hom.:

144333

Cov.:

AF XY:

0.442

AC XY:

321232

AN XY:

726412

show subpopulations

Gnomad4 AFR exome

AF:

0.721

Gnomad4 AMR exome

AF:

0.483

Gnomad4 ASJ exome

AF:

0.484

Gnomad4 EAS exome

AF:

0.364

Gnomad4 SAS exome

AF:

0.524

Gnomad4 FIN exome

AF:

0.435

Gnomad4 NFE exome

AF:

0.425

Gnomad4 OTH exome

AF:

0.450

GnomAD4 genome

AF:

0.519

AC:

78809

AN:

151818

Hom.:

21622

Cov.:

AF XY:

0.518

AC XY:

38425

AN XY:

74160

show subpopulations

Gnomad4 AFR

AF:

0.717

Gnomad4 AMR

AF:

0.498

Gnomad4 ASJ

AF:

0.492

Gnomad4 EAS

AF:

0.355

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.414

Gnomad4 NFE

AF:

0.433

Gnomad4 OTH

AF:

0.507

Alfa

AF:

0.457

Hom.:

9276

Bravo

AF:

0.529

Asia WGS

AF:

0.432

AC:

1502

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	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

- -

Autosomal recessive congenital ichthyosis 4A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

-0.78

Cadd

Benign

Dann

Benign

0.43

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