2-214932324-T-C

Variant names:

• chr2-214932324-T-C
• rs368041060
• NM_173076.3:c.*310A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_173076.3(ABCA12):​c.*310A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 305,556 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (5 hom.)
• Consequence: ABCA12 NM_173076.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.450
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 2-214932324-T-C is Benign according to our data. Variant chr2-214932324-T-C is described in ClinVar as Benign. ClinVar VariationId is 334217.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000814 (124/152332) while in subpopulation SAS AF = 0.0253 (122/4828). AF 95% confidence interval is 0.0216. There are 4 homozygotes in GnomAd4. There are 98 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.*310A>G		3_prime_UTR	Exon 53 of 53	NP_775099.2
	ABCA12	NM_015657.4		c.*310A>G		3_prime_UTR	Exon 45 of 45	NP_056472.2
	ABCA12	NR_103740.2		n.8596A>G		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.*310A>G		3_prime_UTR	Exon 53 of 53	ENSP00000272895.7	Q86UK0-1
	SNHG31	ENST00000607412.2	TSL:2	n.351-15501T>C		intron	N/A
	SNHG31	ENST00000655899.1		n.370-28069T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000808 AC: 123 AN: 152214 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0250

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00298 AC: 456 AN: 153224 Hom.: 5 Cov.: 0 AF XY: 0.00455 AC XY: 371 AN XY: 81466

African (AFR) AF: 0.000473 AC: 2 AN: 4226

American (AMR) AF: 0.00 AC: 0 AN: 5662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4396

East Asian (EAS) AF: 0.000130 AC: 1 AN: 7698

South Asian (SAS) AF: 0.0203 AC: 438 AN: 21580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7296

Middle Eastern (MID) AF: 0.00173 AC: 1 AN: 578

European-Non Finnish (NFE) AF: 0.0000321 AC: 3 AN: 93370

Other (OTH) AF: 0.00131 AC: 11 AN: 8418

GnomAD4 genome AF: 0.000814 AC: 124 AN: 152332 Hom.: 4 Cov.: 32 AF XY: 0.00132 AC XY: 98 AN XY: 74488

African (AFR) AF: 0.0000241 AC: 1 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0253 AC: 122 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000139 Hom.: 0

Bravo AF: 0.0000831

Asia WGS AF: 0.0120 AC: 41 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital ichthyosis of skin (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	15
DANN	Benign	0.87
PhyloP100		0.45
Mutation Taster		=98/2	polymorphism

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: rs368041060; hg19: chr2-215797048;