5-102459786-A-G

Variant names:

• chr5-102459786-A-G
• rs11746217
• NM_173488.5:c.900-9T>C

Variant summary

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

The NM_173488.5(SLCO6A1):​c.900-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,552,550 control chromosomes in the GnomAD database, including 330,201 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 0.65 (31865 hom., cov: 30)
  • Exomes 𝑓: 0.65 (298336 hom.)
• Consequence: SLCO6A1 NM_173488.5 intron
• Scores: Splicing: ADA: 0.00008920
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 15 publications found

Genes affected

SLCO6A1 (HGNC:23613): (solute carrier organic anion transporter family member 6A1) Predicted to enable sodium-independent organic anion transmembrane transporter activity. Predicted to be involved in sodium-independent organic anion transport. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be integral component of 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO6A1	NM_173488.5	c.900-9T>C		intron_variant	Intron 4 of 13	ENST00000506729.6	NP_775759.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO6A1	ENST00000506729.6	c.900-9T>C		intron_variant	Intron 4 of 13	1	NM_173488.5	ENSP00000421339.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 97855 AN: 151322 Hom.: 31842 Cov.: 30

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.629

GnomAD2 exomes AF: 0.642 AC: 125218 AN: 195130 AF XY: 0.642

Gnomad AFR exome AF: 0.671

Gnomad AMR exome AF: 0.576

Gnomad ASJ exome AF: 0.731

Gnomad EAS exome AF: 0.476

Gnomad FIN exome AF: 0.720

Gnomad NFE exome AF: 0.661

Gnomad OTH exome AF: 0.632

GnomAD4 exome AF: 0.650 AC: 910304 AN: 1401108 Hom.: 298336 Cov.: 31 AF XY: 0.648 AC XY: 452018 AN XY: 697256

African (AFR) AF: 0.674 AC: 19727 AN: 29290

American (AMR) AF: 0.576 AC: 16600 AN: 28834

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 16856 AN: 23302

East Asian (EAS) AF: 0.458 AC: 17316 AN: 37788

South Asian (SAS) AF: 0.606 AC: 46958 AN: 77502

European-Finnish (FIN) AF: 0.714 AC: 37098 AN: 51948

Middle Eastern (MID) AF: 0.627 AC: 3423 AN: 5460

European-Non Finnish (NFE) AF: 0.657 AC: 715632 AN: 1089442

Other (OTH) AF: 0.638 AC: 36694 AN: 57542

GnomAD4 genome AF: 0.647 AC: 97921 AN: 151442 Hom.: 31865 Cov.: 30 AF XY: 0.648 AC XY: 47934 AN XY: 73946

African (AFR) AF: 0.665 AC: 27497 AN: 41328

American (AMR) AF: 0.576 AC: 8753 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2444 AN: 3464

East Asian (EAS) AF: 0.456 AC: 2346 AN: 5142

South Asian (SAS) AF: 0.598 AC: 2864 AN: 4790

European-Finnish (FIN) AF: 0.732 AC: 7615 AN: 10400

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.653 AC: 44294 AN: 67804

Other (OTH) AF: 0.624 AC: 1313 AN: 2104

Alfa AF: 0.647 Hom.: 61334

Bravo AF: 0.640

Asia WGS AF: 0.522 AC: 1810 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.59
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000089
dbscSNV1_RF	Benign	0.038
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: rs11746217; hg19: chr5-101795490; COSMIC: COSV107487770;