rs1046482

Variant names:

• chr15-65053624-G-T
• rs1046482
• NM_016563.4:c.*1275C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-65053624-G-T
• chr15-65053624-G-A
• chr15-65053624-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016563.4(RASL12):​c.*1275C>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 0.872 in 989,792 control chromosomes in the GnomAD database, including 376,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.88 (59083 hom., cov: 32)
  • Exomes 𝑓: 0.87 (317177 hom.)
• Consequence: RASL12 NM_016563.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741
• Publications: 8 publications found

Genes affected

RASL12 (HGNC:30289): (RAS like family 12) Predicted to enable GDP binding activity; GTP binding activity; and GTPase activity. Predicted to be involved in signal transduction. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC51B (HGNC:29956): (SLC51 subunit beta) Predicted to enable protein heterodimerization activity and transmembrane transporter activity. Involved in bile acid secretion. Located in basolateral plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC51B Gene-Disease associations (from GenCC):

• bile acid malabsorption, primary, 2

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016563.4. 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
	RASL12	NM_016563.4	MANE Select	c.*1275C>A		3_prime_UTR	Exon 5 of 5	NP_057647.1	Q9NYN1-1
	RASL12	NM_001379429.1		c.*1275C>A		3_prime_UTR	Exon 5 of 5	NP_001366358.1	Q9NYN1-2
	RASL12	NM_001307930.2		c.*1275C>A		3_prime_UTR	Exon 4 of 4	NP_001294859.1	Q9NYN1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASL12	ENST00000220062.9	TSL:1 MANE Select	c.*1275C>A		3_prime_UTR	Exon 5 of 5	ENSP00000220062.4	Q9NYN1-1
	SLC51B	ENST00000334287.3	TSL:2 MANE Select	c.*460G>T		downstream_gene	N/A	ENSP00000335292.2	Q86UW2
	SLC51B	ENST00000886654.1		c.*460G>T		downstream_gene	N/A	ENSP00000556713.1

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133915 AN: 152122 Hom.: 59030 Cov.: 32

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.878

GnomAD4 exome AF: 0.870 AC: 728879 AN: 837552 Hom.: 317177 Cov.: 45 AF XY: 0.870 AC XY: 336887 AN XY: 387176

African (AFR) AF: 0.890 AC: 14076 AN: 15820

American (AMR) AF: 0.867 AC: 1333 AN: 1538

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 4638 AN: 5190

East Asian (EAS) AF: 0.990 AC: 3677 AN: 3716

South Asian (SAS) AF: 0.915 AC: 15403 AN: 16832

European-Finnish (FIN) AF: 0.891 AC: 627 AN: 704

Middle Eastern (MID) AF: 0.876 AC: 1424 AN: 1626

European-Non Finnish (NFE) AF: 0.868 AC: 663593 AN: 764678

Other (OTH) AF: 0.878 AC: 24108 AN: 27448

GnomAD4 genome AF: 0.880 AC: 134026 AN: 152240 Hom.: 59083 Cov.: 32 AF XY: 0.881 AC XY: 65610 AN XY: 74454

African (AFR) AF: 0.895 AC: 37155 AN: 41522

American (AMR) AF: 0.862 AC: 13190 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3083 AN: 3472

East Asian (EAS) AF: 0.985 AC: 5095 AN: 5170

South Asian (SAS) AF: 0.916 AC: 4419 AN: 4826

European-Finnish (FIN) AF: 0.881 AC: 9354 AN: 10612

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.864 AC: 58752 AN: 68026

Other (OTH) AF: 0.879 AC: 1857 AN: 2112

Alfa AF: 0.869 Hom.: 64116

Bravo AF: 0.882

Asia WGS AF: 0.920 AC: 3201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.78
PhyloP100		-0.74
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: rs1046482; hg19: chr15-65345962;