rs7232679

Variant names:

• chr18-3214920-G-C
• rs7232679
• NM_003803.4:c.290+14C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-3214920-G-C
• chr18-3214920-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003803.4(MYOM1):​c.290+14C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,561,468 control chromosomes in the GnomAD database, including 62,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7115 hom., cov: 32)
  • Exomes 𝑓: 0.28 (55647 hom.)
• Consequence: MYOM1 NM_003803.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.224
• Publications: 7 publications found

Genes affected

MYOM1 (HGNC:7613): (myomesin 1) The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD (myomesin 1) and 165 kD (myomesin 2). This protein, myomesin 1, like myomesin 2, titin, and other myofibrillar proteins contains structural modules with strong homology to either fibronectin type III (motif I) or immunoglobulin C2 (motif II) domains. Myomesin 1 and myomesin 2 each have a unique N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the titin string extends into the center of the M band. The integrating structure of the sarcomere arises from muscle-specific members of the superfamily of immunoglobulin-like proteins. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MYOM1 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000265399 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-3214920-G-C is Benign according to our data. Variant chr18-3214920-G-C is described in ClinVar as Benign. ClinVar VariationId is 226816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM1	NM_003803.4	c.290+14C>G		intron_variant	Intron 2 of 37	ENST00000356443.9	NP_003794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOM1	ENST00000356443.9	c.290+14C>G		intron_variant	Intron 2 of 37	1	NM_003803.4	ENSP00000348821.4
MYOM1	ENST00000261606.11	c.290+14C>G		intron_variant	Intron 2 of 36	1		ENSP00000261606.7
ENSG00000265399	ENST00000580139.1	n.198-2072G>C		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45801 AN: 151962 Hom.: 7105 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.277

GnomAD2 exomes AF: 0.272 AC: 57611 AN: 212082 AF XY: 0.270

Gnomad AFR exome AF: 0.377

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.217

Gnomad EAS exome AF: 0.205

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.277

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.279 AC: 392524 AN: 1409388 Hom.: 55647 Cov.: 32 AF XY: 0.278 AC XY: 193077 AN XY: 694242

African (AFR) AF: 0.374 AC: 12106 AN: 32382

American (AMR) AF: 0.218 AC: 8719 AN: 40060

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 4954 AN: 22890

East Asian (EAS) AF: 0.236 AC: 9211 AN: 39072

South Asian (SAS) AF: 0.300 AC: 23627 AN: 78870

European-Finnish (FIN) AF: 0.307 AC: 15474 AN: 50340

Middle Eastern (MID) AF: 0.175 AC: 754 AN: 4300

European-Non Finnish (NFE) AF: 0.279 AC: 301803 AN: 1083552

Other (OTH) AF: 0.274 AC: 15876 AN: 57922

GnomAD4 genome AF: 0.301 AC: 45852 AN: 152080 Hom.: 7115 Cov.: 32 AF XY: 0.301 AC XY: 22363 AN XY: 74350

African (AFR) AF: 0.379 AC: 15718 AN: 41476

American (AMR) AF: 0.261 AC: 3986 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 734 AN: 3468

East Asian (EAS) AF: 0.220 AC: 1135 AN: 5162

South Asian (SAS) AF: 0.303 AC: 1459 AN: 4814

European-Finnish (FIN) AF: 0.305 AC: 3229 AN: 10574

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18675 AN: 67984

Other (OTH) AF: 0.272 AC: 575 AN: 2112

Alfa AF: 0.277 Hom.: 1152

Bravo AF: 0.296

Asia WGS AF: 0.279 AC: 970 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

290+14C>G in intron 2 of MYOM1: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 35.1% (1424/4058) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wa shington.edu/EVS; dbSNP rs7232679). -

Hypertrophic cardiomyopathy Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.15
PhyloP100		-0.22
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7232679; hg19: chr18-3214918; COSMIC: COSV55285247;