7-136992241-T-C

Position:

• chr7-136992241-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001006630.2(CHRM2):​c.-70T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 152,294 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (178 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CHRM2 NM_001006630.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00400

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 7-136992241-T-C is Benign according to our data. Variant chr7-136992241-T-C is described in ClinVar as [Benign]. Clinvar id is 1288157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-70T>C		5_prime_UTR_variant	3/4	ENST00000680005.1	NP_001006631.1
LOC349160	NR_046103.1	n.341+40553A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-70T>C		5_prime_UTR_variant	3/4		NM_001006630.2	ENSP00000505686	P1
	ENST00000586239.5	n.273+40553A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6896 AN: 152176 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.0662

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0721

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0492

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0453 AC: 6899 AN: 152294 Hom.: 178 Cov.: 32 AF XY: 0.0450 AC XY: 3351 AN XY: 74468

Gnomad4 AFR AF: 0.0361

Gnomad4 AMR AF: 0.0296

Gnomad4 ASJ AF: 0.0662

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0734

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0551

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0496 Hom.: 69

Bravo AF: 0.0429

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 27, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.7
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs36210736; hg19: chr7-136676988;