2-215023900-T-G

Variant names:

• chr2-215023900-T-G
• rs952718
• NM_173076.3:c.1287+1773A>C

Variant summary

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

The ENST00000272895.12(ABCA12):​c.1287+1773A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,162 control chromosomes in the GnomAD database, including 46,906 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 0.75 (46906 hom., cov: 32)
• Consequence: ABCA12 ENST00000272895.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.982
• Publications: 10 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

LOC124906117 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000272895.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA12	NM_173076.3	MANE Select	c.1287+1773A>C		intron	N/A	NP_775099.2
	ABCA12	NM_015657.4		c.333+1773A>C		intron	N/A	NP_056472.2
	ABCA12	NR_103740.2		n.1729+1773A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA12	ENST00000272895.12	TSL:1 MANE Select	c.1287+1773A>C		intron	N/A	ENSP00000272895.7
	ABCA12	ENST00000389661.4	TSL:1	c.333+1773A>C		intron	N/A	ENSP00000374312.4
	ENSG00000227769	ENST00000419251.3	TSL:5	n.373+674T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113929 AN: 152044 Hom.: 46899 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.749 AC: 113953 AN: 152162 Hom.: 46906 Cov.: 32 AF XY: 0.753 AC XY: 56005 AN XY: 74404

African (AFR) AF: 0.378 AC: 15670 AN: 41462

American (AMR) AF: 0.738 AC: 11276 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3046 AN: 3472

East Asian (EAS) AF: 0.953 AC: 4924 AN: 5168

South Asian (SAS) AF: 0.839 AC: 4053 AN: 4830

European-Finnish (FIN) AF: 0.968 AC: 10278 AN: 10620

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.913 AC: 62084 AN: 68012

Other (OTH) AF: 0.765 AC: 1614 AN: 2110

Alfa AF: 0.710 Hom.: 18888

Bravo AF: 0.716

Asia WGS AF: 0.874 AC: 3040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.2
DANN	Benign	0.77
PhyloP100		0.98
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: rs952718; hg19: chr2-215888624;