6-37463981-T-C

Variant names:

• chr6-37463981-T-C
• rs2776906
• NM_015050.3:c.1505+973T>C

Variant summary

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

The NM_015050.3(CMTR1):​c.1505+973T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,092 control chromosomes in the GnomAD database, including 39,802 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 0.72 (39802 hom., cov: 32)
• Consequence: CMTR1 NM_015050.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345
• Publications: 6 publications found

Genes affected

CMTR1 (HGNC:21077): (cap methyltransferase 1) Enables mRNA (nucleoside-2'-O-)-methyltransferase activity. Involved in 7-methylguanosine mRNA capping and cap1 mRNA methylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015050.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTR1	NM_015050.3	MANE Select	c.1505+973T>C		intron	N/A	NP_055865.1	Q8N1G2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTR1	ENST00000373451.9	TSL:1 MANE Select	c.1505+973T>C		intron	N/A	ENSP00000362550.4	Q8N1G2
	CMTR1	ENST00000857636.1		c.1505+973T>C		intron	N/A	ENSP00000527695.1
	CMTR1	ENST00000949610.1		c.1523+973T>C		intron	N/A	ENSP00000619669.1

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109145 AN: 151972 Hom.: 39749 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.731

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

GnomAD4 genome AF: 0.718 AC: 109254 AN: 152092 Hom.: 39802 Cov.: 32 AF XY: 0.711 AC XY: 52813 AN XY: 74330

African (AFR) AF: 0.817 AC: 33916 AN: 41506

American (AMR) AF: 0.727 AC: 11107 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2723 AN: 3470

East Asian (EAS) AF: 0.442 AC: 2284 AN: 5162

South Asian (SAS) AF: 0.576 AC: 2777 AN: 4820

European-Finnish (FIN) AF: 0.632 AC: 6664 AN: 10552

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47318 AN: 67980

Other (OTH) AF: 0.726 AC: 1532 AN: 2110

Alfa AF: 0.704 Hom.: 159840

Bravo AF: 0.731

Asia WGS AF: 0.508 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.81
DANN	Benign	0.51
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2776906; hg19: chr6-37431757;