rs2372479

Variant names:

• chr2-215077767-T-G
• rs2372479
• NM_173076.3:c.164-13548A>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.164-13548A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 152,142 control chromosomes in the GnomAD database, including 19,628 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 0.47 (19628 hom., cov: 33)
• Consequence: ABCA12 NM_173076.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 7 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]

ABCA12 Gene-Disease associations (from GenCC):

• autosomal recessive congenital ichthyosis 4B

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, PanelApp Australia, Orphanet, G2P
• autosomal recessive congenital ichthyosis 4A

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital non-bullous ichthyosiform erythroderma

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000227769 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA12	NM_173076.3	c.164-13548A>C		intron_variant	Intron 2 of 52	ENST00000272895.12	NP_775099.2
ABCA12	NR_103740.2	n.582-13548A>C		intron_variant	Intron 2 of 54
ABCA12	XM_011510951.3	c.164-13548A>C		intron_variant	Intron 2 of 52		XP_011509253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12	c.164-13548A>C		intron_variant	Intron 2 of 52	1	NM_173076.3	ENSP00000272895.7
ABCA12	ENST00000412081.1	c.164-2150A>C		intron_variant	Intron 2 of 2	2		ENSP00000400231.1
ENSG00000227769	ENST00000626771.1	n.339-3000T>G		intron_variant	Intron 4 of 5	5
ENSG00000227769	ENST00000628464.2	n.1022-3000T>G		intron_variant	Intron 7 of 8	5

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71982 AN: 152026 Hom.: 19605 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.473 AC: 72032 AN: 152142 Hom.: 19628 Cov.: 33 AF XY: 0.478 AC XY: 35536 AN XY: 74386

African (AFR) AF: 0.196 AC: 8146 AN: 41542

American (AMR) AF: 0.554 AC: 8460 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1906 AN: 3466

East Asian (EAS) AF: 0.266 AC: 1380 AN: 5180

South Asian (SAS) AF: 0.627 AC: 3022 AN: 4822

European-Finnish (FIN) AF: 0.606 AC: 6414 AN: 10578

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.602 AC: 40927 AN: 67966

Other (OTH) AF: 0.471 AC: 994 AN: 2112

Alfa AF: 0.568 Hom.: 12284

Bravo AF: 0.451

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.53
PhyloP100		-0.16
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: rs2372479; hg19: chr2-215942490;