rs77729645

Variant names:

• chr2-214932149-A-G
• rs77729645
• NM_173076.3:c.*485T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_173076.3(ABCA12):​c.*485T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 201,578 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (50 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (0 hom.)
• Consequence: ABCA12 NM_173076.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-214932149-A-G is Benign according to our data. Variant chr2-214932149-A-G is described in ClinVar as Benign. ClinVar VariationId is 334214.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0148 (2259/152296) while in subpopulation AFR AF = 0.0505 (2097/41552). AF 95% confidence interval is 0.0487. There are 50 homozygotes in GnomAd4. There are 1067 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 50 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.*485T>C		3_prime_UTR	Exon 53 of 53	NP_775099.2
	ABCA12	NM_015657.4		c.*485T>C		3_prime_UTR	Exon 45 of 45	NP_056472.2
	ABCA12	NR_103740.2		n.8771T>C		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.*485T>C		3_prime_UTR	Exon 53 of 53	ENSP00000272895.7	Q86UK0-1
	SNHG31	ENST00000607412.2	TSL:2	n.351-15676A>G		intron	N/A
	SNHG31	ENST00000655899.1		n.370-28244A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2252 AN: 152178 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.000812 AC: 40 AN: 49282 Hom.: 0 Cov.: 0 AF XY: 0.000586 AC XY: 15 AN XY: 25618

African (AFR) AF: 0.0313 AC: 17 AN: 544

American (AMR) AF: 0.00267 AC: 9 AN: 3370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 926

East Asian (EAS) AF: 0.00 AC: 0 AN: 2264

South Asian (SAS) AF: 0.000150 AC: 1 AN: 6664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 168

European-Non Finnish (NFE) AF: 0.000230 AC: 7 AN: 30498

Other (OTH) AF: 0.00237 AC: 6 AN: 2528

GnomAD4 genome AF: 0.0148 AC: 2259 AN: 152296 Hom.: 50 Cov.: 32 AF XY: 0.0143 AC XY: 1067 AN XY: 74480

African (AFR) AF: 0.0505 AC: 2097 AN: 41552

American (AMR) AF: 0.00595 AC: 91 AN: 15292

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

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

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68030

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

Alfa AF: 0.00873 Hom.: 13

Bravo AF: 0.0166

Asia WGS AF: 0.00318 AC: 11 AN: 3478

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	-0.83
CADD	Benign	2.6
DANN	Benign	0.49
PhyloP100		1.2
Mutation Taster		=100/0	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: rs77729645; hg19: chr2-215796873;