rs380400

Variant names:

• chr3-148742913-G-A
• rs380400
• NM_000685.5:c.*798G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-148742913-G-A
• chr3-148742913-G-T

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.*798G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 166,080 control chromosomes in the GnomAD database, including 47,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (42990 hom., cov: 31)
  • Exomes 𝑓: 0.82 (4858 hom.)
• Consequence: AGTR1 NM_000685.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.446
• Publications: 9 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=-0.83).
• BP6: Variant 3-148742913-G-A is Benign according to our data. Variant chr3-148742913-G-A is described in ClinVar as Benign. ClinVar VariationId is 343686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.864 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.*798G>A		3_prime_UTR	Exon 3 of 3	NP_000676.1	P30556
	AGTR1	NM_001382736.1		c.*798G>A		3_prime_UTR	Exon 2 of 2	NP_001369665.1	Q53YY0
	AGTR1	NM_001382737.1		c.*798G>A		3_prime_UTR	Exon 3 of 3	NP_001369666.1	P30556

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	ENST00000349243.8	TSL:1 MANE Select	c.*798G>A		3_prime_UTR	Exon 3 of 3	ENSP00000273430.3	P30556
	AGTR1	ENST00000404754.2	TSL:1	c.*798G>A		3_prime_UTR	Exon 2 of 2	ENSP00000385612.2	P30556
	AGTR1	ENST00000497524.5	TSL:1	c.*798G>A		3_prime_UTR	Exon 2 of 2	ENSP00000419422.1	P30556

Frequencies

GnomAD3 genomes AF: 0.719 AC: 108924 AN: 151512 Hom.: 42977 Cov.: 31

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.770

GnomAD4 exome AF: 0.819 AC: 11843 AN: 14452 Hom.: 4858 Cov.: 0 AF XY: 0.820 AC XY: 5616 AN XY: 6852

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AF: 1.00 AC: 4 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.750 AC: 3 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.819 AC: 11678 AN: 14262

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.864 AC: 76 AN: 88

Other (OTH) AF: 0.886 AC: 78 AN: 88

GnomAD4 genome AF: 0.719 AC: 108954 AN: 151628 Hom.: 42990 Cov.: 31 AF XY: 0.719 AC XY: 53319 AN XY: 74132

African (AFR) AF: 0.359 AC: 14827 AN: 41258

American (AMR) AF: 0.856 AC: 13036 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 3131 AN: 3466

East Asian (EAS) AF: 0.838 AC: 4340 AN: 5176

South Asian (SAS) AF: 0.697 AC: 3350 AN: 4804

European-Finnish (FIN) AF: 0.819 AC: 8599 AN: 10502

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.870 AC: 59071 AN: 67890

Other (OTH) AF: 0.773 AC: 1630 AN: 2110

Alfa AF: 0.837 Hom.: 44805

Bravo AF: 0.710

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Renal tubular dysgenesis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.36
PhyloP100		-0.45
Mutation Taster		=100/0	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: rs380400; hg19: chr3-148460700;