7-136869276-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001006630.2(CHRM2):​c.-267G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00653 in 152,590 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 7 hom., cov: 32)
Exomes 𝑓: 0.0069 ( 0 hom. )

Consequence

CHRM2
NM_001006630.2 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.610
Variant links:
Genes affected
CHRM2 (HGNC:1951): (cholinergic receptor muscarinic 2) The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine to these receptors and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The muscarinic cholinergic receptor 2 is involved in mediation of bradycardia and a decrease in cardiac contractility. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 7-136869276-G-A is Benign according to our data. Variant chr7-136869276-G-A is described in ClinVar as [Benign]. Clinvar id is 384721.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CHRM2NM_001006630.2 linkuse as main transcriptc.-267G>A 5_prime_UTR_variant 2/4 ENST00000680005.1 NP_001006631.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHRM2ENST00000680005.1 linkuse as main transcriptc.-267G>A 5_prime_UTR_variant 2/4 NM_001006630.2 ENSP00000505686 P1
ENST00000586239.5 linkuse as main transcriptn.274-83385C>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00654
AC:
996
AN:
152184
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00200
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00550
Gnomad ASJ
AF:
0.00605
Gnomad EAS
AF:
0.00657
Gnomad SAS
AF:
0.00393
Gnomad FIN
AF:
0.00179
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.0103
Gnomad OTH
AF:
0.0120
GnomAD4 exome
AF:
0.00694
AC:
2
AN:
288
Hom.:
0
Cov.:
0
AF XY:
0.00952
AC XY:
2
AN XY:
210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00820
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00653
AC:
995
AN:
152302
Hom.:
7
Cov.:
32
AF XY:
0.00606
AC XY:
451
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.00200
Gnomad4 AMR
AF:
0.00549
Gnomad4 ASJ
AF:
0.00605
Gnomad4 EAS
AF:
0.00659
Gnomad4 SAS
AF:
0.00393
Gnomad4 FIN
AF:
0.00179
Gnomad4 NFE
AF:
0.0103
Gnomad4 OTH
AF:
0.0118
Alfa
AF:
0.00662
Hom.:
1
Bravo
AF:
0.00693
Asia WGS
AF:
0.00520
AC:
18
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxOct 26, 2016This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
9.9
DANN
Benign
0.88

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139124053; hg19: chr7-136554023; API