2-214969952-A-G

Variant names:

• chr2-214969952-A-G
• rs3795857
• NM_173076.3:c.5690+321T>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.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
• Publications: 3 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: G2P, Genomics England PanelApp, Orphanet
• autosomal recessive congenital ichthyosis 4A

  Inheritance: AR Classification: STRONG Submitted by: 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

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA12	NM_173076.3	MANE Select	c.5690+321T>C		intron	N/A	NP_775099.2
	ABCA12	NM_015657.4		c.4736+321T>C		intron	N/A	NP_056472.2
	ABCA12	NR_103740.2		n.6188+321T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA12	ENST00000272895.12	TSL:1 MANE Select	c.5690+321T>C		intron	N/A	ENSP00000272895.7	Q86UK0-1
	ABCA12	ENST00000389661.4	TSL:1	c.4736+321T>C		intron	N/A	ENSP00000374312.4	Q86UK0-2

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

African (AFR) AF: 0.483 AC: 20000 AN: 41408

American (AMR) AF: 0.540 AC: 8233 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1752 AN: 3462

East Asian (EAS) AF: 0.266 AC: 1374 AN: 5158

South Asian (SAS) AF: 0.521 AC: 2506 AN: 4810

European-Finnish (FIN) AF: 0.544 AC: 5727 AN: 10532

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 34963 AN: 67802

Other (OTH) AF: 0.482 AC: 1017 AN: 2110

Alfa AF: 0.499 Hom.: 9458

Bravo AF: 0.495

Asia WGS AF: 0.396 AC: 1377 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.5
DANN	Benign	0.90
PhyloP100		0.77
Mutation Taster		=99/1	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: rs3795857; hg19: chr2-215834676;