NM_000685.5:c.-47-1134T>C

Variant names:

• chr3-148739855-T-C
• rs1800766
• NM_000685.5:c.-47-1134T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000685.5(AGTR1):​c.-47-1134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,231,686 control chromosomes in the GnomAD database, including 16,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1585 hom., cov: 32)
  • Exomes 𝑓: 0.16 (14718 hom.)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.868
• Publications: 21 publications found

Genes affected

AGTR1 (HGNC:336): (angiotensin II receptor type 1) Angiotensin II is a potent vasopressor hormone and a primary regulator of aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. It acts through at least two types of receptors. This gene encodes the type 1 receptor which is thought to mediate the major cardiovascular effects of angiotensin II. This gene may play a role in the generation of reperfusion arrhythmias following restoration of blood flow to ischemic or infarcted myocardium. It was previously thought that a related gene, denoted as AGTR1B, existed; however, it is now believed that there is only one type 1 receptor gene in humans. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2020]

AGTR1 Gene-Disease associations (from GenCC):

• renal tubular dysgenesis of genetic origin

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• essential hypertension, genetic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-148739855-T-C is Benign according to our data. Variant chr3-148739855-T-C is described in ClinVar as Benign. ClinVar VariationId is 1278984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000685.5. 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
	AGTR1	NM_000685.5	MANE Select	c.-47-1134T>C		intron	N/A	NP_000676.1	P30556
	AGTR1	NM_032049.4		c.-149T>C		5_prime_UTR	Exon 3 of 4	NP_114438.3	Q53YY0
	AGTR1	NM_001382736.1		c.-47-1134T>C		intron	N/A	NP_001369665.1	Q53YY0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	ENST00000349243.8	TSL:1 MANE Select	c.-47-1134T>C		intron	N/A	ENSP00000273430.3	P30556
	AGTR1	ENST00000404754.2	TSL:1	c.-47-1134T>C		intron	N/A	ENSP00000385612.2	P30556
	AGTR1	ENST00000497524.5	TSL:1	c.-47-1134T>C		intron	N/A	ENSP00000419422.1	P30556

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21498 AN: 152128 Hom.: 1584 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.163 AC: 175828 AN: 1079440 Hom.: 14718 Cov.: 31 AF XY: 0.163 AC XY: 83165 AN XY: 509564

African (AFR) AF: 0.100 AC: 2299 AN: 22964

American (AMR) AF: 0.115 AC: 972 AN: 8418

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 3656 AN: 14390

East Asian (EAS) AF: 0.160 AC: 4231 AN: 26520

South Asian (SAS) AF: 0.132 AC: 2581 AN: 19494

European-Finnish (FIN) AF: 0.118 AC: 2481 AN: 21102

Middle Eastern (MID) AF: 0.240 AC: 701 AN: 2918

European-Non Finnish (NFE) AF: 0.165 AC: 151638 AN: 919962

Other (OTH) AF: 0.166 AC: 7269 AN: 43672

GnomAD4 genome AF: 0.141 AC: 21506 AN: 152246 Hom.: 1585 Cov.: 32 AF XY: 0.137 AC XY: 10200 AN XY: 74444

African (AFR) AF: 0.102 AC: 4250 AN: 41542

American (AMR) AF: 0.121 AC: 1843 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 821 AN: 3472

East Asian (EAS) AF: 0.156 AC: 807 AN: 5172

South Asian (SAS) AF: 0.134 AC: 647 AN: 4830

European-Finnish (FIN) AF: 0.110 AC: 1165 AN: 10616

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11352 AN: 68006

Other (OTH) AF: 0.152 AC: 321 AN: 2110

Alfa AF: 0.160 Hom.: 3595

Bravo AF: 0.142

Asia WGS AF: 0.138 AC: 482 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.37
DANN	Benign	0.54
PhyloP100		-0.87
PromoterAI		0.014	Neutral
Mutation Taster		=296/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800766; hg19: chr3-148457642;