2-214969952-A-G

Position:

• chr2-214969952-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173076.3(ABCA12):​c.5690+321T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,728 control chromosomes in the GnomAD database, including 19,380 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 0.50 (19380 hom., cov: 31)
• Consequence: ABCA12 NM_173076.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA12	NM_173076.3	c.5690+321T>C		intron_variant		ENST00000272895.12
ABCA12	NM_015657.4	c.4736+321T>C		intron_variant
ABCA12	XM_011510951.3	c.5699+321T>C		intron_variant
ABCA12	NR_103740.2	n.6188+321T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA12	ENST00000272895.12	c.5690+321T>C		intron_variant		1	NM_173076.3	P1
ABCA12	ENST00000389661.4	c.4736+321T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76172 AN: 151612 Hom.: 19354 Cov.: 31

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.503 AC: 76245 AN: 151728 Hom.: 19380 Cov.: 31 AF XY: 0.503 AC XY: 37281 AN XY: 74108

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.482

Alfa AF: 0.497 Hom.: 8421

Bravo AF: 0.495

Asia WGS AF: 0.396 AC: 1377 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.5
DANN	Benign	0.90

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: rs3795857; hg19: chr2-215834676;