3-148740989-G-A

Position:

• chr3-148740989-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000685.5(AGTR1):​c.-47G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: AGTR1 NM_000685.5 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.07967
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.445

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23807955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-47G>A		5_prime_UTR_premature_start_codon_gain_variant	3/3	ENST00000349243.8	NP_000676.1
AGTR1	NM_000685.5	c.-47G>A		splice_region_variant	3/3	ENST00000349243.8	NP_000676.1
AGTR1	NM_000685.5	c.-47G>A		5_prime_UTR_variant	3/3	ENST00000349243.8	NP_000676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243	c.-47G>A		5_prime_UTR_premature_start_codon_gain_variant	3/3	1	NM_000685.5	ENSP00000273430.3
AGTR1	ENST00000349243.8	c.-47G>A		splice_region_variant	3/3	1	NM_000685.5	ENSP00000273430.3
AGTR1	ENST00000349243	c.-47G>A		5_prime_UTR_variant	3/3	1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Renal tubular dysgenesis of genetic origin;CN305331:Essential hypertension, genetic Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.0056	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.62
DEOGEN2	Benign	0.24	T;T
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.42	T;T
MetaRNN	Benign	0.24	T;T
PrimateAI	Benign	0.30	T
Vest4		0.18
MVP		0.78
GERP RS		3.5
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.080
dbscSNV1_RF	Benign	0.29
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-148458776; COSMIC: COSV62557738;