chr3-148729969-G-A

Variant names:

• chr3-148729969-G-A
• rs388915
• NM_000685.5:c.-47-11020G>A

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.-47-11020G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 287,234 control chromosomes in the GnomAD database, including 71,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (34036 hom., cov: 29)
  • Exomes 𝑓: 0.74 (37310 hom.)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.29
• Publications: 13 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.91).
• BP6: Variant 3-148729969-G-A is Benign according to our data. Variant chr3-148729969-G-A is described in ClinVar as Benign. ClinVar VariationId is 1233874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	NM_000685.5	MANE Select	c.-47-11020G>A		intron	N/A	NP_000676.1
	AGTR1	NM_001382736.1		c.-47-11020G>A		intron	N/A	NP_001369665.1
	AGTR1	NM_001382737.1		c.-47-11020G>A		intron	N/A	NP_001369666.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	ENST00000349243.8	TSL:1 MANE Select	c.-47-11020G>A		intron	N/A	ENSP00000273430.3
	AGTR1	ENST00000404754.2	TSL:1	c.-47-11020G>A		intron	N/A	ENSP00000385612.2
	AGTR1	ENST00000497524.5	TSL:1	c.-47-11020G>A		intron	N/A	ENSP00000419422.1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98372 AN: 151566 Hom.: 34019 Cov.: 29

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.675

GnomAD4 exome AF: 0.737 AC: 99872 AN: 135550 Hom.: 37310 AF XY: 0.737 AC XY: 51122 AN XY: 69366

African (AFR) AF: 0.379 AC: 1637 AN: 4314

American (AMR) AF: 0.777 AC: 3050 AN: 3926

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 3695 AN: 5350

East Asian (EAS) AF: 0.846 AC: 10973 AN: 12970

South Asian (SAS) AF: 0.821 AC: 966 AN: 1176

European-Finnish (FIN) AF: 0.810 AC: 8008 AN: 9888

Middle Eastern (MID) AF: 0.664 AC: 482 AN: 726

European-Non Finnish (NFE) AF: 0.734 AC: 64531 AN: 87956

Other (OTH) AF: 0.706 AC: 6530 AN: 9244

GnomAD4 genome AF: 0.649 AC: 98412 AN: 151684 Hom.: 34036 Cov.: 29 AF XY: 0.659 AC XY: 48848 AN XY: 74144

African (AFR) AF: 0.377 AC: 15554 AN: 41254

American (AMR) AF: 0.758 AC: 11548 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2436 AN: 3464

East Asian (EAS) AF: 0.842 AC: 4339 AN: 5156

South Asian (SAS) AF: 0.833 AC: 3999 AN: 4802

European-Finnish (FIN) AF: 0.805 AC: 8484 AN: 10544

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.734 AC: 49847 AN: 67928

Other (OTH) AF: 0.679 AC: 1428 AN: 2102

Alfa AF: 0.707 Hom.: 30652

Bravo AF: 0.631

Asia WGS AF: 0.811 AC: 2818 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.66
PhyloP100		-1.3
PromoterAI		0.016	Neutral
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: rs388915; hg19: chr3-148447756;