15-65051748-C-T

Variant names:

• chr15-65051748-C-T
• rs4238399
• NM_178859.4:c.188+143C>T

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+143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 642,918 control chromosomes in the GnomAD database, including 57,249 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 0.36 (11042 hom., cov: 30)
  • Exomes 𝑓: 0.41 (46207 hom.)
• Consequence: SLC51B NM_178859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• Publications: 5 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 = 0.764 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC51B	NM_178859.4	MANE Select	c.188+143C>T		intron	N/A	NP_849190.2	Q86UW2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC51B	ENST00000334287.3	TSL:2 MANE Select	c.188+143C>T		intron	N/A	ENSP00000335292.2	Q86UW2
	SLC51B	ENST00000886654.1		c.188+143C>T		intron	N/A	ENSP00000556713.1
	SLC51B	ENST00000886655.1		c.188+143C>T		intron	N/A	ENSP00000556714.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 54338 AN: 149276 Hom.: 11029 Cov.: 30

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.415 AC: 204671 AN: 493524 Hom.: 46207 AF XY: 0.411 AC XY: 107273 AN XY: 261148

African (AFR) AF: 0.187 AC: 2419 AN: 12940

American (AMR) AF: 0.485 AC: 9586 AN: 19782

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 4782 AN: 13604

East Asian (EAS) AF: 0.809 AC: 23682 AN: 29278

South Asian (SAS) AF: 0.337 AC: 16637 AN: 49360

European-Finnish (FIN) AF: 0.408 AC: 15569 AN: 38154

Middle Eastern (MID) AF: 0.347 AC: 863 AN: 2484

European-Non Finnish (NFE) AF: 0.399 AC: 120520 AN: 301696

Other (OTH) AF: 0.405 AC: 10613 AN: 26226

GnomAD4 genome AF: 0.364 AC: 54366 AN: 149394 Hom.: 11042 Cov.: 30 AF XY: 0.370 AC XY: 26965 AN XY: 72866

African (AFR) AF: 0.195 AC: 7770 AN: 39864

American (AMR) AF: 0.460 AC: 6932 AN: 15058

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1169 AN: 3430

East Asian (EAS) AF: 0.784 AC: 4019 AN: 5128

South Asian (SAS) AF: 0.352 AC: 1636 AN: 4652

European-Finnish (FIN) AF: 0.424 AC: 4394 AN: 10374

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.402 AC: 27156 AN: 67630

Other (OTH) AF: 0.382 AC: 787 AN: 2060

Alfa AF: 0.374 Hom.: 2663

Bravo AF: 0.360

Asia WGS AF: 0.505 AC: 1751 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	1.4
DANN	Benign	0.63
PhyloP100		0.33
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: rs4238399; hg19: chr15-65344086;