6-159897771-A-G

Variant names:

• chr6-159897771-A-G
• rs220733
• NM_002377.4:c.-243-1415A>G

Variant summary

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

The NM_002377.4(MAS1):​c.-243-1415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.985 in 152,344 control chromosomes in the GnomAD database, including 73,969 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 0.99 (73969 hom., cov: 32)
• Consequence: MAS1 NM_002377.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 3 publications found

Genes affected

MAS1 (HGNC:6899): (MAS1 proto-oncogene, G protein-coupled receptor) This gene encodes a class I seven-transmembrane G-protein-coupled receptor. The encoded protein is a receptor for angiotensin-(1-7) and preferentially couples to the Gq protein, activating the phospholipase C signaling pathway. The encoded protein may play a role in multiple processes including hypotension, smooth muscle relaxation and cardioprotection by mediating the effects of angiotensin-(1-7). [provided by RefSeq, May 2012]

ENSG00000236823 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAS1	NM_002377.4	c.-243-1415A>G		intron_variant	Intron 1 of 2	ENST00000674077.2	NP_002368.1
MAS1	NM_001366704.2	c.-37+6588A>G		intron_variant	Intron 1 of 1		NP_001353633.1
MAS1	XM_047418776.1	c.-243-1415A>G		intron_variant	Intron 2 of 3		XP_047274732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAS1	ENST00000674077.2	c.-243-1415A>G		intron_variant	Intron 1 of 2		NM_002377.4	ENSP00000501180.2
ENSG00000236823	ENST00000434562.2	n.147-1415A>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.985 AC: 149994 AN: 152226 Hom.: 73910 Cov.: 32

Gnomad AFR AF: 0.997

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.978

Gnomad OTH AF: 0.987

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

GnomAD4 genome AF: 0.985 AC: 150112 AN: 152344 Hom.: 73969 Cov.: 32 AF XY: 0.986 AC XY: 73475 AN XY: 74502

African (AFR) AF: 0.997 AC: 41449 AN: 41576

American (AMR) AF: 0.982 AC: 15025 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3368 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5188

South Asian (SAS) AF: 0.997 AC: 4814 AN: 4830

European-Finnish (FIN) AF: 0.986 AC: 10473 AN: 10620

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.978 AC: 66508 AN: 68036

Other (OTH) AF: 0.987 AC: 2088 AN: 2116

Alfa AF: 0.980 Hom.: 9262

Bravo AF: 0.985

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.52
DANN	Benign	0.41
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs220733; hg19: chr6-160318803;