NM_173076.3:c.*26G>A

Variant names:

• chr2-214932608-C-T
• rs17426207
• NM_173076.3:c.*26G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173076.3(ABCA12):​c.*26G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,524,524 control chromosomes in the GnomAD database, including 128,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12214 hom., cov: 32)
  • Exomes 𝑓: 0.41 (116741 hom.)
• Consequence: ABCA12 NM_173076.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.787

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]

SNHG31 (HGNC:54196): (small nucleolar RNA host gene 31)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 2-214932608-C-T is Benign according to our data. Variant chr2-214932608-C-T is described in ClinVar as [Benign]. Clinvar id is 334218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-214932608-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA12	NM_173076.3	c.*26G>A		3_prime_UTR_variant	Exon 53 of 53	ENST00000272895.12	NP_775099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895	c.*26G>A		3_prime_UTR_variant	Exon 53 of 53	1	NM_173076.3	ENSP00000272895.7

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60741 AN: 151852 Hom.: 12209 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.390

GnomAD3 exomes AF: 0.421 AC: 104291 AN: 247654 Hom.: 22232 AF XY: 0.427 AC XY: 57160 AN XY: 133830

Gnomad AFR exome AF: 0.347

Gnomad AMR exome AF: 0.440

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.340

Gnomad SAS exome AF: 0.522

Gnomad FIN exome AF: 0.425

Gnomad NFE exome AF: 0.409

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.409 AC: 561683 AN: 1372554 Hom.: 116741 Cov.: 21 AF XY: 0.413 AC XY: 284359 AN XY: 687962

Gnomad4 AFR exome AF: 0.348

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.449

Gnomad4 EAS exome AF: 0.364

Gnomad4 SAS exome AF: 0.526

Gnomad4 FIN exome AF: 0.432

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.400 AC: 60783 AN: 151970 Hom.: 12214 Cov.: 32 AF XY: 0.405 AC XY: 30048 AN XY: 74266

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.389

Alfa AF: 0.405 Hom.: 3286

Bravo AF: 0.392

Asia WGS AF: 0.405 AC: 1410 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive congenital ichthyosis 4A Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital ichthyosis of skin Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal recessive congenital ichthyosis 4B Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.36
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs17426207; hg19: chr2-215797332; COSMIC: COSV55955768; COSMIC: COSV55955768;