chr11-75164072-C-G

Variant names:

• chr11-75164072-C-G
• rs140953109
• NM_007256.5:c.257C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007256.5(SLCO2B1):​c.257C>G​(p.Thr86Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T86M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLCO2B1 NM_007256.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 2 publications found

Genes affected

SLCO2B1 (HGNC:10962): (solute carrier organic anion transporter family member 2B1) This locus encodes a member of the organic anion-transporting polypeptide family of membrane proteins. The protein encoded by this locus may function in regulation of placental uptake of sulfated steroids. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO2B1	NM_007256.5	c.257C>G	p.Thr86Arg	missense_variant	Exon 3 of 14	ENST00000289575.10	NP_009187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO2B1	ENST00000289575.10	c.257C>G	p.Thr86Arg	missense_variant	Exon 3 of 14	1	NM_007256.5	ENSP00000289575.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Uncertain	0.98
Eigen	Benign	0.15
Eigen_PC	Benign	0.0026
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.88	D;T;T;T;.
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.64	D;D;D;D;D
MetaSVM	Benign	-0.59	T
PhyloP100		2.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.6	D;N;D;D;N
REVEL	Uncertain	0.44
Sift	Benign	0.15	T;D;T;T;D
Sift4G	Benign	0.21	T;D;T;T;T
Vest4		0.64, 0.64
MutPred		0.61		.;Gain of methylation at T86 (P = 0.0439);.;.;.;
MVP		0.81
MPC		0.88
ClinPred		0.97	D
GERP RS		1.8
gMVP		0.64
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs140953109; hg19: chr11-74875117;