chr11-75165906-G-A

Variant names:

• chr11-75165906-G-A
• rs1109407
• NM_007256.5:c.405G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_007256.5(SLCO2B1):​c.405G>A​(p.Pro135Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,614,038 control chromosomes in the GnomAD database, including 355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (200 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (155 hom.)
• Consequence: SLCO2B1 NM_007256.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.03
• Publications: 5 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 11-75165906-G-A is Benign according to our data. Variant chr11-75165906-G-A is described in ClinVar as [Benign]. Clinvar id is 783634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO2B1	NM_007256.5	c.405G>A	p.Pro135Pro	synonymous_variant	Exon 4 of 14	ENST00000289575.10	NP_009187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO2B1	ENST00000289575.10	c.405G>A	p.Pro135Pro	synonymous_variant	Exon 4 of 14	1	NM_007256.5	ENSP00000289575.5

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4164 AN: 152140 Hom.: 200 Cov.: 33

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00743 AC: 1867 AN: 251362 AF XY: 0.00554

Gnomad AFR exome AF: 0.0993

Gnomad AMR exome AF: 0.00541

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00269 AC: 3936 AN: 1461780 Hom.: 155 Cov.: 31 AF XY: 0.00234 AC XY: 1701 AN XY: 727200

African (AFR) AF: 0.0934 AC: 3125 AN: 33476

American (AMR) AF: 0.00588 AC: 263 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5764

European-Non Finnish (NFE) AF: 0.000122 AC: 136 AN: 1111976

Other (OTH) AF: 0.00599 AC: 362 AN: 60392

GnomAD4 genome AF: 0.0274 AC: 4174 AN: 152258 Hom.: 200 Cov.: 33 AF XY: 0.0264 AC XY: 1967 AN XY: 74446

African (AFR) AF: 0.0955 AC: 3968 AN: 41536

American (AMR) AF: 0.00928 AC: 142 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68010

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.0110 Hom.: 225

Bravo AF: 0.0313

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.41
DANN	Benign	0.77
PhyloP100		-4.0
PromoterAI		0.037	Neutral
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: rs1109407; hg19: chr11-74876951;