2-215009882-A-G

Variant names:

• chr2-215009882-A-G
• rs6758257
• NM_173076.3:c.2472+449T>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.2472+449T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,154 control chromosomes in the GnomAD database, including 46,758 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 (46758 hom., cov: 33)
• Consequence: ABCA12 NM_173076.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536
• Publications: 0 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=-0.83).
• 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: NM_173076.3. 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.2472+449T>C		intron	N/A	NP_775099.2
	ABCA12	NM_015657.4		c.1518+449T>C		intron	N/A	NP_056472.2
	ABCA12	NR_103740.2		n.2914+449T>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.2472+449T>C		intron	N/A	ENSP00000272895.7
	ABCA12	ENST00000389661.4	TSL:1	c.1518+449T>C		intron	N/A	ENSP00000374312.4
	ENSG00000227769	ENST00000617699.1	TSL:5	n.29-3174A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113617 AN: 152036 Hom.: 46752 Cov.: 33

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.747 AC: 113644 AN: 152154 Hom.: 46758 Cov.: 33 AF XY: 0.751 AC XY: 55873 AN XY: 74420

African (AFR) AF: 0.373 AC: 15485 AN: 41486

American (AMR) AF: 0.735 AC: 11209 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3042 AN: 3468

East Asian (EAS) AF: 0.953 AC: 4937 AN: 5182

South Asian (SAS) AF: 0.840 AC: 4056 AN: 4826

European-Finnish (FIN) AF: 0.967 AC: 10274 AN: 10624

Middle Eastern (MID) AF: 0.769 AC: 223 AN: 290

European-Non Finnish (NFE) AF: 0.912 AC: 62027 AN: 67992

Other (OTH) AF: 0.761 AC: 1611 AN: 2116

Alfa AF: 0.822 Hom.: 6763

Bravo AF: 0.714

Asia WGS AF: 0.872 AC: 3025 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		0.54
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: rs6758257; hg19: chr2-215874606;