15-65051697-G-A

Variant names:

• chr15-65051697-G-A
• rs2946676
• NM_178859.4:c.188+92G>A

Variant summary

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

The NM_178859.4(SLC51B):​c.188+92G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,190,930 control chromosomes in the GnomAD database, including 463,788 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 0.89 (60428 hom., cov: 29)
  • Exomes 𝑓: 0.88 (403360 hom.)
• Consequence: SLC51B NM_178859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 6 publications found

Genes affected

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]

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]

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 = 0.965 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC51B	NM_178859.4	MANE Select	c.188+92G>A		intron	N/A	NP_849190.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC51B	ENST00000334287.3	TSL:2 MANE Select	c.188+92G>A		intron	N/A	ENSP00000335292.2
	SLC51B	ENST00000886654.1		c.188+92G>A		intron	N/A	ENSP00000556713.1
	SLC51B	ENST00000886655.1		c.188+92G>A		intron	N/A	ENSP00000556714.1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135320 AN: 151902 Hom.: 60375 Cov.: 29

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.884

GnomAD4 exome AF: 0.881 AC: 915126 AN: 1038910 Hom.: 403360 AF XY: 0.882 AC XY: 468441 AN XY: 531210

African (AFR) AF: 0.924 AC: 22977 AN: 24878

American (AMR) AF: 0.878 AC: 33144 AN: 37756

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 19920 AN: 22206

East Asian (EAS) AF: 0.979 AC: 35109 AN: 35868

South Asian (SAS) AF: 0.921 AC: 68735 AN: 74640

European-Finnish (FIN) AF: 0.873 AC: 43367 AN: 49690

Middle Eastern (MID) AF: 0.862 AC: 4090 AN: 4744

European-Non Finnish (NFE) AF: 0.871 AC: 646897 AN: 742960

Other (OTH) AF: 0.886 AC: 40887 AN: 46168

GnomAD4 genome AF: 0.891 AC: 135431 AN: 152020 Hom.: 60428 Cov.: 29 AF XY: 0.891 AC XY: 66230 AN XY: 74314

African (AFR) AF: 0.924 AC: 38290 AN: 41448

American (AMR) AF: 0.868 AC: 13251 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3092 AN: 3472

East Asian (EAS) AF: 0.988 AC: 5108 AN: 5172

South Asian (SAS) AF: 0.921 AC: 4421 AN: 4802

European-Finnish (FIN) AF: 0.883 AC: 9348 AN: 10582

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58942 AN: 67966

Other (OTH) AF: 0.885 AC: 1858 AN: 2100

Alfa AF: 0.874 Hom.: 8028

Bravo AF: 0.894

Asia WGS AF: 0.925 AC: 3216 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	0.62
DANN	Benign	0.66
PhyloP100		-0.42
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: rs2946676; hg19: chr15-65344035;