Genetic Variant RASL12:c.*1275C>A (chr15-65053624-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.88 ( 59083 hom., cov: 32)

Exomes 𝑓: 0.87 ( 317177 hom. )

Consequence

RASL12
NM_016563.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.741

Publications

8 publications found

Variant links:

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]

RASL12 links:

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: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

SLC51B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASL12	NM_016563.4 link	c.*1275C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000220062.9	NP_057647.1
SLC51B	NM_178859.4 link	c.*460G>T		downstream_gene_variant		ENST00000334287.3	NP_849190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASL12	ENST00000220062.9 link	c.*1275C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_016563.4	ENSP00000220062.4
SLC51B	ENST00000334287.3 link	c.*460G>T		downstream_gene_variant		2	NM_178859.4	ENSP00000335292.2

Frequencies

GnomAD3 genomes

AF:

0.880

AC:

133915

AN:

152122

Hom.:

59030

Cov.:

show subpopulations

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.:

AF XY:

0.870

AC XY:

336887

AN XY:

387176

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

5674

11348

17023

22697

28371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19952

39904

59856

79808

99760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.880

AC:

134026

AN:

152240

Hom.:

59083

Cov.:

AF XY:

0.881

AC XY:

65610

AN XY:

74454

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

823

1646

2470

3293

4116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.36

(source)

DANN

Benign

0.78

PhyloP100

-0.74

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over