NM_173076.3:c.1956+106G>A

Variant names:

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

Variant summary

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

The NM_173076.3(ABCA12):​c.1956+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 1,164,322 control chromosomes in the GnomAD database, including 494,702 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 0.80 (52160 hom., cov: 32)
  • Exomes 𝑓: 0.93 (442542 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, 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA12	NM_173076.3	c.1956+106G>A		intron_variant	Intron 15 of 52	ENST00000272895.12	NP_775099.2
ABCA12	NM_015657.4	c.1002+106G>A		intron_variant	Intron 7 of 44		NP_056472.2
ABCA12	NR_103740.2	n.2398+106G>A		intron_variant	Intron 16 of 54
ABCA12	XM_011510951.3	c.1956+106G>A		intron_variant	Intron 15 of 52		XP_011509253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12	c.1956+106G>A		intron_variant	Intron 15 of 52	1	NM_173076.3	ENSP00000272895.7
ABCA12	ENST00000389661.4	c.1002+106G>A		intron_variant	Intron 7 of 44	1		ENSP00000374312.4
ENSG00000227769	ENST00000617699.1	n.190+2167C>T		intron_variant	Intron 2 of 3	5
ENSG00000227769	ENST00000627811.1	n.73+2167C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121436 AN: 152000 Hom.: 52162 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.827

GnomAD4 exome AF: 0.931 AC: 942344 AN: 1012204 Hom.: 442542 AF XY: 0.933 AC XY: 477833 AN XY: 511958

African (AFR) AF: 0.431 AC: 9924 AN: 23046

American (AMR) AF: 0.781 AC: 24431 AN: 31282

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 19722 AN: 21752

East Asian (EAS) AF: 1.00 AC: 33506 AN: 33516

South Asian (SAS) AF: 0.940 AC: 63551 AN: 67634

European-Finnish (FIN) AF: 0.976 AC: 44348 AN: 45446

Middle Eastern (MID) AF: 0.861 AC: 3079 AN: 3578

European-Non Finnish (NFE) AF: 0.949 AC: 703426 AN: 741186

Other (OTH) AF: 0.902 AC: 40357 AN: 44764

GnomAD4 genome AF: 0.798 AC: 121459 AN: 152118 Hom.: 52160 Cov.: 32 AF XY: 0.802 AC XY: 59638 AN XY: 74392

African (AFR) AF: 0.452 AC: 18726 AN: 41394

American (AMR) AF: 0.788 AC: 12033 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3168 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5185 AN: 5190

South Asian (SAS) AF: 0.943 AC: 4548 AN: 4822

European-Finnish (FIN) AF: 0.974 AC: 10346 AN: 10622

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64616 AN: 68022

Other (OTH) AF: 0.828 AC: 1749 AN: 2112

Alfa AF: 0.817 Hom.: 2206

Bravo AF: 0.773

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.55
PhyloP100		0.14
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: rs6753310; hg19: chr2-215880108;