rs2071406

Positions:

• chr1-230714895-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000412344.1(ENSG00000244137):​n.381-4042T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,230 control chromosomes in the GnomAD database, including 2,039 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 0.13 (2039 hom., cov: 32)
• Consequence: ENST00000412344.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594

Genes affected

(HGNC:):

AGT (HGNC:333): (angiotensinogen) The protein encoded by this gene, pre-angiotensinogen or angiotensinogen precursor, is expressed in the liver and is cleaved by the enzyme renin in response to lowered blood pressure. The resulting product, angiotensin I, is then cleaved by angiotensin converting enzyme (ACE) to generate the physiologically active enzyme angiotensin II. The protein is involved in maintaining blood pressure, body fluid and electrolyte homeostasis, and in the pathogenesis of essential hypertension and preeclampsia. Mutations in this gene are associated with susceptibility to essential hypertension, and can cause renal tubular dysgenesis, a severe disorder of renal tubular development. Defects in this gene have also been associated with non-familial structural atrial fibrillation, and inflammatory bowel disease. [provided by RefSeq, Nov 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001382817.3	c.-30-4042T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000412344.1	n.381-4042T>C		intron_variant, non_coding_transcript_variant		3
AGT	ENST00000681269.1	c.-30-4042T>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20028 AN: 152112 Hom.: 2030 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.132 AC: 20079 AN: 152230 Hom.: 2039 Cov.: 32 AF XY: 0.133 AC XY: 9934 AN XY: 74434

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0792

Gnomad4 NFE AF: 0.0487

Gnomad4 OTH AF: 0.142

Alfa AF: 0.0740 Hom.: 693

Bravo AF: 0.148

Asia WGS AF: 0.159 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.5
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071406; hg19: chr1-230850641;