3-148730631-A-G

Variant names:

• chr3-148730631-A-G
• rs12695902
• NM_000685.5:c.-47-10358A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000685.5(AGTR1):​c.-47-10358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 155,928 control chromosomes in the GnomAD database, including 552 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.082 (538 hom., cov: 32)
  • Exomes 𝑓: 0.084 (14 hom.)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0927 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.-47-10358A>G		intron	N/A	NP_000676.1	P30556
	AGTR1	NM_001382736.1		c.-47-10358A>G		intron	N/A	NP_001369665.1	Q53YY0
	AGTR1	NM_001382737.1		c.-47-10358A>G		intron	N/A	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.-47-10358A>G		intron	N/A	ENSP00000273430.3	P30556
	AGTR1	ENST00000404754.2	TSL:1	c.-47-10358A>G		intron	N/A	ENSP00000385612.2	P30556
	AGTR1	ENST00000497524.5	TSL:1	c.-47-10358A>G		intron	N/A	ENSP00000419422.1	P30556

Frequencies

GnomAD3 genomes AF: 0.0821 AC: 12486 AN: 152142 Hom.: 538 Cov.: 32

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0700

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.0798

GnomAD4 exome AF: 0.0842 AC: 309 AN: 3668 Hom.: 14 AF XY: 0.0850 AC XY: 156 AN XY: 1836

African (AFR) AF: 0.0944 AC: 17 AN: 180

American (AMR) AF: 0.0568 AC: 5 AN: 88

Ashkenazi Jewish (ASJ) AF: 0.0422 AC: 7 AN: 166

East Asian (EAS) AF: 0.00 AC: 0 AN: 204

South Asian (SAS) AF: 0.0833 AC: 3 AN: 36

European-Finnish (FIN) AF: 0.0674 AC: 12 AN: 178

Middle Eastern (MID) AF: 0.115 AC: 3 AN: 26

European-Non Finnish (NFE) AF: 0.0961 AC: 239 AN: 2488

Other (OTH) AF: 0.0762 AC: 23 AN: 302

GnomAD4 genome AF: 0.0820 AC: 12489 AN: 152260 Hom.: 538 Cov.: 32 AF XY: 0.0802 AC XY: 5971 AN XY: 74434

African (AFR) AF: 0.0821 AC: 3409 AN: 41542

American (AMR) AF: 0.0698 AC: 1067 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0675 AC: 234 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.0307 AC: 148 AN: 4828

European-Finnish (FIN) AF: 0.0898 AC: 953 AN: 10608

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0947 AC: 6440 AN: 68026

Other (OTH) AF: 0.0785 AC: 166 AN: 2114

Alfa AF: 0.0909 Hom.: 1175

Bravo AF: 0.0809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		0.15
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: rs12695902; hg19: chr3-148448418;