Genetic Variant SUCNR1:p.Leu65Leu (chr3-151880738-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_033050.6(SUCNR1):c.195C>T(p.Leu65Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,614,080 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 31 hom. )

Consequence

SUCNR1
NM_033050.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.367

Variant links:

Genes affected

SUCNR1 (HGNC:4542): (succinate receptor 1) This gene encodes a G-protein-coupled receptor for succinate, an intermediate molecule of the citric acid cycle. It is involved in the promotion of hematopoietic progenitor cell development, and it has a potential role in renovascular hypertension which has known correlations to renal failure, diabetes and atherosclerosis. [provided by RefSeq, Oct 2009]

SUCNR1 links:

AADACL2-AS1 (HGNC:50301): (AADACL2 antisense RNA 1)

AADACL2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 3-151880738-C-T is Benign according to our data. Variant chr3-151880738-C-T is described in ClinVar as [Benign]. Clinvar id is 713065.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.367 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00165 (251/152284) while in subpopulation EAS AF= 0.0374 (194/5188). AF 95% confidence interval is 0.0331. There are 3 homozygotes in gnomad4. There are 146 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCNR1	NM_033050.6 link	c.195C>T	p.Leu65Leu	synonymous_variant	Exon 3 of 3	ENST00000362032.6	NP_149039.2	Q9BXA5
AADACL2-AS1	NR_110202.1 link	n.319+47119G>A		intron_variant	Intron 1 of 3
AADACL2-AS1	NR_110203.1 link	n.319+47119G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SUCNR1	ENST00000362032.6 link	c.195C>T	p.Leu65Leu	synonymous_variant	Exon 3 of 3	1	NM_033050.6	ENSP00000355156.4	Q9BXA5
AADACL2-AS1	ENST00000475855.1 link	n.319+47119G>A		intron_variant	Intron 1 of 3	5
AADACL2-AS1	ENST00000483843.6 link	n.439+36877G>A		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.00166

AC:

253

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0375

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00363

AC:

913

AN:

251284

Hom.:

AF XY:

0.00370

AC XY:

502

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0400

Gnomad SAS exome

AF:

0.00392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00144

AC:

2103

AN:

1461796

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

1162

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0354

Gnomad4 SAS exome

AF:

0.00432

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000168

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00165

AC:

251

AN:

152284

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

146

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0374

Gnomad4 SAS

AF:

0.00683

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000194

Hom.:

Bravo

AF:

0.00182

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

3.9

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over