7-136868746-GCACACACACACACACA-G

Position:

• chr7-136868746-GCACACACACACACACA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001006630.2(CHRM2):​c.-516_-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 0.0737 in 149,562 control chromosomes in the GnomAD database, including 516 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.074 (516 hom., cov: 0)
  • Exomes 𝑓: 0.015 (0 hom.)
• Consequence: CHRM2 NM_001006630.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.33

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-GCACACACACACACACA-G is Benign according to our data. Variant chr7-136868746-GCACACACACACACACA-G is described in ClinVar as [Benign]. Clinvar id is 1271139.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-516_-501del		5_prime_UTR_variant	1/4	ENST00000680005.1	NP_001006631.1
CHRM2	NM_001006627.3	c.-438_-423del		5_prime_UTR_variant	1/3		NP_001006628.1
CHRM2	NM_001378972.1	c.-628_-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.-516_-501del		5_prime_UTR_variant	1/4		NM_001006630.2	ENSP00000505686	P1
	ENST00000586239.5	n.274-82871_274-82856del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11016 AN: 149262 Hom.: 515 Cov.: 0

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.000607

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0823

GnomAD4 exome AF: 0.0155 AC: 3 AN: 194 Hom.: 0 AF XY: 0.0185 AC XY: 3 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: 0.0174

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0738 AC: 11018 AN: 149368 Hom.: 516 Cov.: 0 AF XY: 0.0713 AC XY: 5192 AN XY: 72794

Gnomad4 AFR AF: 0.0228

Gnomad4 AMR AF: 0.0653

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.000609

Gnomad4 SAS AF: 0.0730

Gnomad4 FIN AF: 0.0762

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.0383 Hom.: 771

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;