3-148729969-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000685.5(AGTR1):​c.-47-11020G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000735 in 136,004 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000074 (0 hom.)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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>T		intron	N/A	NP_000676.1
	AGTR1	NM_001382736.1		c.-47-11020G>T		intron	N/A	NP_001369665.1
	AGTR1	NM_001382737.1		c.-47-11020G>T		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>T		intron	N/A	ENSP00000273430.3
	AGTR1	ENST00000404754.2	TSL:1	c.-47-11020G>T		intron	N/A	ENSP00000385612.2
	AGTR1	ENST00000497524.5	TSL:1	c.-47-11020G>T		intron	N/A	ENSP00000419422.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000735 AC: 1 AN: 136004 Hom.: 0 AF XY: 0.0000144 AC XY: 1 AN XY: 69628

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 4334

American (AMR) AF: 0.00 AC: 0 AN: 3942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5366

East Asian (EAS) AF: 0.00 AC: 0 AN: 13002

South Asian (SAS) AF: 0.00 AC: 0 AN: 1184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 726

European-Non Finnish (NFE) AF: 0.0000113 AC: 1 AN: 88264

Other (OTH) AF: 0.00 AC: 0 AN: 9276

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.56
PhyloP100		-1.3
PromoterAI		0.013	Neutral

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;