chr1-7849677-C-T

Position:

• chr1-7849677-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_006786.4(UTS2):​c.221G>A​(p.Ser74Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 1,607,856 control chromosomes in the GnomAD database, including 4,932 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S74G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.059 (691 hom., cov: 32)
  • Exomes 𝑓: 0.045 (4241 hom.)
• Consequence: UTS2 NM_006786.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480

Genes affected

UTS2 (HGNC:12636): (urotensin 2) This gene encodes a mature peptide that is an active cyclic heptapeptide absolutely conserved from lamprey to human. The active peptide acts as a vasoconstrictor and is expressed only in brain tissue. Despite the gene family name similarity, this gene is not homologous to urocortin, a member of the sauvagine/corticotropin-releasing factor/urotensin I family. Most of the proprotein is cleaved to make the mature peptide. Transcript variants encoding different preproprotein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTS2	NM_006786.4	c.221G>A	p.Ser74Asn	missense_variant	3/4	ENST00000361696.10
UTS2	NM_021995.2	c.266G>A	p.Ser89Asn	missense_variant	4/5
UTS2	XM_011540537.3	c.266G>A	p.Ser89Asn	missense_variant	5/6
UTS2	XM_011540538.2	c.221G>A	p.Ser74Asn	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTS2	ENST00000361696.10	c.221G>A	p.Ser74Asn	missense_variant	3/4	1	NM_006786.4	P2
UTS2	ENST00000054668.5	c.266G>A	p.Ser89Asn	missense_variant	4/5	1		A2
UTS2	ENST00000377516.6	c.221G>A	p.Ser74Asn	missense_variant	4/7	5

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9025 AN: 152122 Hom.: 688 Cov.: 32

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.00915

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0300

Gnomad OTH AF: 0.0627

GnomAD3 exomes AF: 0.0875 AC: 21533 AN: 246126 Hom.: 2585 AF XY: 0.0766 AC XY: 10206 AN XY: 133318

Gnomad AFR exome AF: 0.0474

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.0370

Gnomad EAS exome AF: 0.279

Gnomad SAS exome AF: 0.0475

Gnomad FIN exome AF: 0.0114

Gnomad NFE exome AF: 0.0286

Gnomad OTH exome AF: 0.0637

GnomAD4 exome AF: 0.0448 AC: 65145 AN: 1455616 Hom.: 4241 Cov.: 30 AF XY: 0.0438 AC XY: 31713 AN XY: 724264

Gnomad4 AFR exome AF: 0.0477

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.0375

Gnomad4 EAS exome AF: 0.245

Gnomad4 SAS exome AF: 0.0502

Gnomad4 FIN exome AF: 0.0134

Gnomad4 NFE exome AF: 0.0286

Gnomad4 OTH exome AF: 0.0541

GnomAD4 genome AF: 0.0594 AC: 9039 AN: 152240 Hom.: 691 Cov.: 32 AF XY: 0.0629 AC XY: 4684 AN XY: 74430

Gnomad4 AFR AF: 0.0471

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.0363

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.0540

Gnomad4 FIN AF: 0.00915

Gnomad4 NFE AF: 0.0300

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0452 Hom.: 920

Bravo AF: 0.0774

TwinsUK AF: 0.0275 AC: 102

ALSPAC AF: 0.0283 AC: 109

ESP6500AA AF: 0.0513 AC: 226

ESP6500EA AF: 0.0293 AC: 252

ExAC AF: 0.0830 AC: 10076

Asia WGS AF: 0.178 AC: 618 AN: 3478

EpiCase AF: 0.0311

EpiControl AF: 0.0306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.2
DANN	Benign	0.92
DEOGEN2	Benign	0.098	.;T;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.50	T;T;T
MetaRNN	Benign	0.0094	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.062
Sift	Benign	0.072	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.56	P;B;B
Vest4		0.050
MPC		0.22
ClinPred		0.0028	T
GERP RS		-0.92
Varity_R		0.055
gMVP		0.024

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: 6

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

Publications

LitVar

Other links and lift over

dbSNP: rs2890565; hg19: chr1-7909737; COSMIC: COSV50013136; COSMIC: COSV50013136;