Genetic Variant NM_018949.3:c.543G>A (chr17-82374867-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_018949.3(UTS2R):c.543G>A(p.Thr181Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,331,736 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 49 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 35 hom. )

Consequence

UTS2R
NM_018949.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.63

Publications

1 publications found

Variant links:

Genes affected

UTS2R (HGNC:4468): (urotensin 2 receptor) Predicted to enable urotensin II receptor activity. Predicted to be involved in neuropeptide signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

UTS2R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 17-82374867-G-A is Benign according to our data. Variant chr17-82374867-G-A is described in ClinVar as Benign. ClinVar VariationId is 780472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.63 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.014 (2138/152302) while in subpopulation AFR AF = 0.0486 (2020/41584). AF 95% confidence interval is 0.0468. There are 49 homozygotes in GnomAd4. There are 1013 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018949.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTS2R	NM_018949.3	MANE Select	c.543G>A	p.Thr181Thr	synonymous	Exon 3 of 3	NP_061822.1	Q9UKP6
	UTS2R	NM_001381897.1		c.543G>A	p.Thr181Thr	synonymous	Exon 2 of 2	NP_001368826.1	Q9UKP6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UTS2R	ENST00000313135.5	TSL:6 MANE Select	c.543G>A	p.Thr181Thr	synonymous	Exon 3 of 3	ENSP00000323516.2	Q9UKP6
UTS2R	ENST00000856767.1		c.543G>A	p.Thr181Thr	synonymous	Exon 2 of 2	ENSP00000526826.1
UTS2R	ENST00000923106.1		c.543G>A	p.Thr181Thr	synonymous	Exon 4 of 4	ENSP00000593165.1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2128

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00310

AC:

444

AN:

143020

AF XY:

0.00236

show subpopulations

Gnomad AFR exome

AF:

0.0497

Gnomad AMR exome

AF:

0.00271

Gnomad ASJ exome

AF:

0.000122

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.00147

AC:

1731

AN:

1179434

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

728

AN XY:

591624

show subpopulations

African (AFR)

AF:

0.0483

AC:

1355

AN:

28082

American (AMR)

AF:

0.00293

AC:

107

AN:

36554

Ashkenazi Jewish (ASJ)

AF:

0.0000418

AC:

AN:

23912

East Asian (EAS)

AF:

0.00

AC:

AN:

35462

South Asian (SAS)

AF:

0.000118

AC:

AN:

76526

European-Finnish (FIN)

AF:

0.0000585

AC:

AN:

34204

Middle Eastern (MID)

AF:

0.00239

AC:

AN:

4184

European-Non Finnish (NFE)

AF:

0.0000630

AC:

AN:

889360

Other (OTH)

AF:

0.00373

AC:

191

AN:

51150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

106

211

317

422

528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0140

AC:

2138

AN:

152302

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1013

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0486

AC:

2020

AN:

41584

American (AMR)

AF:

0.00562

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68004

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

105

209

314

418

523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00732

Hom.:

Bravo

AF:

0.0158

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.9

(source)

DANN

Benign

0.91

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over