7-136868746-GCACA-G

Position:

• chr7-136868746-GCACA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001006630.2(CHRM2):​c.-504_-501del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 149,120 control chromosomes in the GnomAD database, including 43 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (43 hom., cov: 0)
  • Exomes 𝑓: 0.041 (0 hom.)
• Consequence: CHRM2 NM_001006630.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.95

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 -10 ACMG points.

• BP6: Variant 7-136868746-GCACA-G is Benign according to our data. Variant chr7-136868746-GCACA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1316263.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0151 (2246/148926) while in subpopulation AFR AF= 0.0461 (1880/40768). AF 95% confidence interval is 0.0444. There are 43 homozygotes in gnomad4. There are 1087 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 43 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-504_-501del		5_prime_UTR_variant	1/4	ENST00000680005.1	NP_001006631.1
CHRM2	NM_001006627.3	c.-426_-423del		5_prime_UTR_variant	1/3		NP_001006628.1
CHRM2	NM_001378972.1	c.-616_-613del		5_prime_UTR_variant	1/5		NP_001365901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-504_-501del		5_prime_UTR_variant	1/4		NM_001006630.2	ENSP00000505686	P1
	ENST00000586239.5	n.274-82859_274-82856del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2237 AN: 148830 Hom.: 43 Cov.: 0

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.00384

Gnomad FIN AF: 0.00152

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.0132

GnomAD4 exome AF: 0.0412 AC: 8 AN: 194 Hom.: 0 AF XY: 0.0370 AC XY: 6 AN XY: 162

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0465

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0151 AC: 2246 AN: 148926 Hom.: 43 Cov.: 0 AF XY: 0.0150 AC XY: 1087 AN XY: 72560

Gnomad4 AFR AF: 0.0461

Gnomad4 AMR AF: 0.00581

Gnomad4 ASJ AF: 0.000292

Gnomad4 EAS AF: 0.0185

Gnomad4 SAS AF: 0.00385

Gnomad4 FIN AF: 0.00152

Gnomad4 NFE AF: 0.00187

Gnomad4 OTH AF: 0.0131

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs35916399; hg19: chr7-136553493;