rs10498027

chr2-214955289-G-Achr2-214955289-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_173076.3(ABCA12):c.6306C>T(p.Tyr2102=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,613,548 control chromosomes in the GnomAD database, including 135,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11635 hom., cov: 33)
  • Exomes 𝑓: 0.41 (123378 hom.)
• Consequence: ABCA12 NM_173076.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.500

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 2-214955289-G-A is Benign according to our data. Variant chr2-214955289-G-A is described in ClinVar as [Benign]. Clinvar id is 262831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-214955289-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.5 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA12	NM_173076.3	c.6306C>T	p.Tyr2102=	synonymous_variant	43/53	ENST00000272895.12
SNHG31	NR_110292.1	n.445-6521G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA12	ENST00000272895.12	c.6306C>T	p.Tyr2102=	synonymous_variant	43/53	1	NM_173076.3	P1
SNHG31	ENST00000670391.1	n.438-6521G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58710 AN: 151908 Hom.: 11625 Cov.: 33

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.418

GnomAD3 exomes AF: 0.406 AC: 101921 AN: 251218 Hom.: 21326 AF XY: 0.412 AC XY: 55919 AN XY: 135774

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.399

Gnomad ASJ exome AF: 0.513

Gnomad EAS exome AF: 0.236

Gnomad SAS exome AF: 0.475

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.417

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.408 AC: 596543 AN: 1461522 Hom.: 123378 Cov.: 42 AF XY: 0.411 AC XY: 298803 AN XY: 727096

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.503

Gnomad4 EAS exome AF: 0.243

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.410

GnomAD4 genome AF: 0.386 AC: 58754 AN: 152026 Hom.: 11635 Cov.: 33 AF XY: 0.387 AC XY: 28744 AN XY: 74314

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.418

Alfa AF: 0.412 Hom.: 22026

Bravo AF: 0.378

Asia WGS AF: 0.356 AC: 1239 AN: 3478

EpiCase AF: 0.422

EpiControl AF: 0.418

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Autosomal recessive congenital ichthyosis 4A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Congenital ichthyosis of skin Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	0.11
Dann	Benign	0.37

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: rs10498027; hg19: chr2-215820013; COSMIC: COSV55978073;