chr3-133936002-G-A

Variant names:

• chr3-133936002-G-A
• rs7616492
• NM_005630.3:c.1691-105C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005630.3(SLCO2A1):​c.1691-105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,198,494 control chromosomes in the GnomAD database, including 79,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (7152 hom., cov: 32)
  • Exomes 𝑓: 0.37 (72437 hom.)
• Consequence: SLCO2A1 NM_005630.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.84
• Publications: 7 publications found

Genes affected

SLCO2A1 (HGNC:10955): (solute carrier organic anion transporter family member 2A1) This gene encodes a prostaglandin transporter that is a member of the 12-membrane-spanning superfamily of transporters. The encoded protein may be involved in mediating the uptake and clearance of prostaglandins in numerous tissues. [provided by RefSeq, Dec 2011]

SLCO2A1 Gene-Disease associations (from GenCC):

• hypertrophic osteoarthropathy, primary, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• hypertrophic osteoarthropathy, primary, autosomal recessive, 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• chronic enteropathy associated with SLCO2A1 gene

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• pachydermoperiostosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-133936002-G-A is Benign according to our data. Variant chr3-133936002-G-A is described in ClinVar as Benign. ClinVar VariationId is 1177670.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005630.3. 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
	SLCO2A1	NM_005630.3	MANE Select	c.1691-105C>T		intron	N/A	NP_005621.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO2A1	ENST00000310926.11	TSL:1 MANE Select	c.1691-105C>T		intron	N/A	ENSP00000311291.4
	SLCO2A1	ENST00000860072.1		c.1730-105C>T		intron	N/A	ENSP00000530131.1
	SLCO2A1	ENST00000860067.1		c.1721-105C>T		intron	N/A	ENSP00000530126.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42264 AN: 152016 Hom.: 7156 Cov.: 32

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.365 AC: 382108 AN: 1046360 Hom.: 72437 AF XY: 0.364 AC XY: 184022 AN XY: 505648

African (AFR) AF: 0.0713 AC: 1733 AN: 24322

American (AMR) AF: 0.301 AC: 5246 AN: 17446

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 5618 AN: 15544

East Asian (EAS) AF: 0.276 AC: 8608 AN: 31134

South Asian (SAS) AF: 0.232 AC: 7991 AN: 34374

European-Finnish (FIN) AF: 0.339 AC: 13461 AN: 39708

Middle Eastern (MID) AF: 0.358 AC: 1183 AN: 3306

European-Non Finnish (NFE) AF: 0.387 AC: 323602 AN: 836986

Other (OTH) AF: 0.337 AC: 14666 AN: 43540

GnomAD4 genome AF: 0.278 AC: 42257 AN: 152134 Hom.: 7152 Cov.: 32 AF XY: 0.274 AC XY: 20379 AN XY: 74370

African (AFR) AF: 0.0802 AC: 3331 AN: 41558

American (AMR) AF: 0.303 AC: 4625 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1197 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1281 AN: 5174

South Asian (SAS) AF: 0.238 AC: 1147 AN: 4826

European-Finnish (FIN) AF: 0.330 AC: 3489 AN: 10574

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26118 AN: 67950

Other (OTH) AF: 0.307 AC: 647 AN: 2108

Alfa AF: 0.351 Hom.: 27688

Bravo AF: 0.272

Asia WGS AF: 0.221 AC: 771 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.019
DANN	Benign	0.81
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7616492; hg19: chr3-133654846; COSMIC: COSV60491140;