2-214932094-A-AC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_173076.3(ABCA12):c.*539_*540insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 164,732 control chromosomes in the GnomAD database, including 1,321 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.072 (1319 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (2 hom.)
• Consequence: ABCA12 NM_173076.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.601

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 -10 ACMG points.

• BP6: Variant 2-214932094-A-AC is Benign according to our data. Variant chr2-214932094-A-AC is described in ClinVar as [Likely_benign]. Clinvar id is 334212.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA12	NM_173076.3	c.*539_*540insG		3_prime_UTR_variant	53/53	ENST00000272895.12
SNHG31	NR_110292.1	n.322-15730dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA12	ENST00000272895.12	c.*539_*540insG		3_prime_UTR_variant	53/53	1	NM_173076.3	P1
SNHG31	ENST00000670391.1	n.438-29715dup		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10891 AN: 152084 Hom.: 1315 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0284

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.0589

GnomAD4 exome AF: 0.00375 AC: 47 AN: 12530 Hom.: 2 Cov.: 0 AF XY: 0.00410 AC XY: 27 AN XY: 6580

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00169

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000879

Gnomad4 OTH exome AF: 0.0107

GnomAD4 genome AF: 0.0717 AC: 10915 AN: 152202 Hom.: 1319 Cov.: 31 AF XY: 0.0693 AC XY: 5156 AN XY: 74426

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.0283

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00110

Gnomad4 OTH AF: 0.0582

Bravo AF: 0.0826

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital ichthyosiform erythroderma Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs139753893; hg19: chr2-215796818;