rs956133

Variant names:

• chr2-214958622-A-G
• rs956133
• NM_173076.3:c.5940-168T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173076.3(ABCA12):​c.5940-168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,042 control chromosomes in the GnomAD database, including 23,566 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23566 hom., cov: 32)
• Consequence: ABCA12 NM_173076.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA12	NM_173076.3	c.5940-168T>C		intron_variant	Intron 40 of 52	ENST00000272895.12	NP_775099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12	c.5940-168T>C		intron_variant	Intron 40 of 52	1	NM_173076.3	ENSP00000272895.7

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82826 AN: 151926 Hom.: 23530 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.533

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.545 AC: 82919 AN: 152042 Hom.: 23566 Cov.: 32 AF XY: 0.546 AC XY: 40609 AN XY: 74328

African (AFR) AF: 0.708 AC: 29383 AN: 41478

American (AMR) AF: 0.544 AC: 8309 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1747 AN: 3464

East Asian (EAS) AF: 0.356 AC: 1837 AN: 5162

South Asian (SAS) AF: 0.605 AC: 2921 AN: 4826

European-Finnish (FIN) AF: 0.450 AC: 4762 AN: 10574

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32169 AN: 67954

Other (OTH) AF: 0.530 AC: 1120 AN: 2114

Alfa AF: 0.499 Hom.: 10082

Bravo AF: 0.551

Asia WGS AF: 0.454 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.55
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs956133; hg19: chr2-215823346;