rs6753310

Variant names:

• chr2-215015384-C-A
• rs6753310
• NM_173076.3:c.1956+106G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-215015384-C-A
• chr2-215015384-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_173076.3(ABCA12):​c.1956+106G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,165,000 control chromosomes in the GnomAD database, including 28 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 0.0081 (18 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (10 hom.)
• Consequence: ABCA12 NM_173076.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• Publications: 1 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, Orphanet, G2P
• autosomal recessive congenital ichthyosis 4A

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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=-0.8).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00812 (1236/152176) while in subpopulation AFR AF = 0.0288 (1194/41438). AF 95% confidence interval is 0.0275. There are 18 homozygotes in GnomAd4. There are 589 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

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.1956+106G>T		intron	N/A	NP_775099.2
	ABCA12	NM_015657.4		c.1002+106G>T		intron	N/A	NP_056472.2
	ABCA12	NR_103740.2		n.2398+106G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA12	ENST00000272895.12	TSL:1 MANE Select	c.1956+106G>T		intron	N/A	ENSP00000272895.7	Q86UK0-1
	ABCA12	ENST00000389661.4	TSL:1	c.1002+106G>T		intron	N/A	ENSP00000374312.4	Q86UK0-2
	ENSG00000227769	ENST00000617699.1	TSL:5	n.190+2167C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00811 AC: 1233 AN: 152058 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.000834 AC: 845 AN: 1012824 Hom.: 10 AF XY: 0.000691 AC XY: 354 AN XY: 512262

African (AFR) AF: 0.0287 AC: 663 AN: 23106

American (AMR) AF: 0.00160 AC: 50 AN: 31330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21768

East Asian (EAS) AF: 0.00 AC: 0 AN: 33518

South Asian (SAS) AF: 0.0000591 AC: 4 AN: 67656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45456

Middle Eastern (MID) AF: 0.00307 AC: 11 AN: 3582

European-Non Finnish (NFE) AF: 0.0000499 AC: 37 AN: 741624

Other (OTH) AF: 0.00179 AC: 80 AN: 44784

GnomAD4 genome AF: 0.00812 AC: 1236 AN: 152176 Hom.: 18 Cov.: 32 AF XY: 0.00791 AC XY: 589 AN XY: 74424

African (AFR) AF: 0.0288 AC: 1194 AN: 41438

American (AMR) AF: 0.00157 AC: 24 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68022

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00 Hom.: 2206

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.48
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6753310;

hg19: chr2-215880108;