20-62754795-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002531.3(NTSR1):c.825A>C(p.Gln275His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,611,518 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.012 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (36 hom.)
• Consequence: NTSR1 NM_002531.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.417

Genes affected

NTSR1 (HGNC:8039): (neurotensin receptor 1) Neurotensin receptor 1 belongs to the large superfamily of G-protein coupled receptors. NTSR1 mediates the multiple functions of neurotensin, such as hypotension, hyperglycemia, hypothermia, antinociception, and regulation of intestinal motility and secretion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002824515).
• BP6: Variant 20-62754795-A-C is Benign according to our data. Variant chr20-62754795-A-C is described in ClinVar as [Benign]. Clinvar id is 769105.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1817/152078) while in subpopulation AFR AF= 0.041 (1699/41458). AF 95% confidence interval is 0.0394. There are 39 homozygotes in gnomad4. There are 844 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTSR1	NM_002531.3	c.825A>C	p.Gln275His	missense_variant	2/4	ENST00000370501.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTSR1	ENST00000370501.4	c.825A>C	p.Gln275His	missense_variant	2/4	1	NM_002531.3	P1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1798 AN: 151960 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00348 AC: 869 AN: 249736 Hom.: 19 AF XY: 0.00246 AC XY: 333 AN XY: 135252

Gnomad AFR exome AF: 0.0447

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00139 AC: 2023 AN: 1459440 Hom.: 36 Cov.: 31 AF XY: 0.00121 AC XY: 881 AN XY: 726156

Gnomad4 AFR exome AF: 0.0435

Gnomad4 AMR exome AF: 0.00302

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000169

Gnomad4 OTH exome AF: 0.00325

GnomAD4 genome AF: 0.0119 AC: 1817 AN: 152078 Hom.: 39 Cov.: 32 AF XY: 0.0113 AC XY: 844 AN XY: 74366

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00197 Hom.: 8

Bravo AF: 0.0136

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0445 AC: 196

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00431 AC: 523

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000357

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	7.9
Dann	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.18
Sift	Benign	0.11	T
Sift4G	Benign	0.58	T
Polyphen		0.79	P
Vest4		0.17
MutPred		0.12		Gain of disorder (P = 0.1027);
MVP		0.52
MPC		0.30
ClinPred		0.020	T
GERP RS		-3.4
Varity_R		0.048
gMVP		0.54

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

LitVar

Other links and lift over

dbSNP: rs35373650; hg19: chr20-61386147;