2-214932608-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 334218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

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.*26G>A		3_prime_UTR	Exon 53 of 53	NP_775099.2
	ABCA12	NM_015657.4		c.*26G>A		3_prime_UTR	Exon 45 of 45	NP_056472.2
	ABCA12	NR_103740.2		n.8312G>A		non_coding_transcript_exon	Exon 55 of 55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA12	ENST00000272895.12	TSL:1 MANE Select	c.*26G>A		3_prime_UTR	Exon 53 of 53	ENSP00000272895.7	Q86UK0-1
	SNHG31	ENST00000607412.2	TSL:2	n.351-15217C>T		intron	N/A
	SNHG31	ENST00000655899.1		n.370-27785C>T		intron	N/A

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

GnomAD2 exomes AF: 0.421 AC: 104291 AN: 247654 AF XY: 0.427

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 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

African (AFR) AF: 0.348 AC: 11029 AN: 31698

American (AMR) AF: 0.437 AC: 19341 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 11473 AN: 25550

East Asian (EAS) AF: 0.364 AC: 14245 AN: 39162

South Asian (SAS) AF: 0.526 AC: 44366 AN: 84344

European-Finnish (FIN) AF: 0.432 AC: 22964 AN: 53166

Middle Eastern (MID) AF: 0.382 AC: 2130 AN: 5576

European-Non Finnish (NFE) AF: 0.400 AC: 413048 AN: 1031404

Other (OTH) AF: 0.402 AC: 23087 AN: 57384

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

African (AFR) AF: 0.352 AC: 14582 AN: 41436

American (AMR) AF: 0.432 AC: 6591 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1596 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1842 AN: 5172

South Asian (SAS) AF: 0.526 AC: 2529 AN: 4808

European-Finnish (FIN) AF: 0.411 AC: 4341 AN: 10556

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27855 AN: 67944

Other (OTH) AF: 0.389 AC: 822 AN: 2114

Alfa AF: 0.405 Hom.: 3286

Bravo AF: 0.392

Asia WGS AF: 0.405 AC: 1410 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal recessive congenital ichthyosis 4A (1)
-	-	1	Autosomal recessive congenital ichthyosis 4B (1)
-	-	1	Congenital ichthyosis of skin (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.36
DANN	Benign	0.68
PhyloP100		-0.79
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: rs17426207; hg19: chr2-215797332; COSMIC: COSV55955768; COSMIC: COSV55955768;