chr2-214947573-G-A

Position:

• chr2-214947573-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.40

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]

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

ACMG classification

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	Protein	UniProt
ABCA12	NM_173076.3	c.7105-17C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000272895.12	NP_775099.2
SNHG31	NR_110292.1	n.322-252G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12	c.7105-17C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_173076.3	ENSP00000272895	P1
SNHG31	ENST00000670391.1	n.438-14237G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78738 AN: 151700 Hom.: 21600 Cov.: 31

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

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.: 40 AF XY: 0.442 AC XY: 321232 AN XY: 726412

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.: 31 AF XY: 0.518 AC XY: 38425 AN XY: 74160

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:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

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

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	12
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

Other links and lift over

dbSNP: rs2274412; hg19: chr2-215812297; COSMIC: COSV55965610;