rs45591233

Variant names:

• chr19-50289427-C-T
• rs45591233
• NM_001145809.2:c.4753-9C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001145809.2(MYH14):​c.4753-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,600,376 control chromosomes in the GnomAD database, including 797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (60 hom., cov: 31)
  • Exomes 𝑓: 0.031 (737 hom.)
• Consequence: MYH14 NM_001145809.2 intron
• Scores: Splicing: ADA: 0.0004698
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0460

Genes affected

MYH14 (HGNC:23212): (myosin heavy chain 14) This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-14 (MYO14). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene result in one form of autosomal dominant hearing impairment. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 19-50289427-C-T is Benign according to our data. Variant chr19-50289427-C-T is described in ClinVar as [Benign]. Clinvar id is 44072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50289427-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0234 (3565/152286) while in subpopulation NFE AF= 0.0349 (2376/68014). AF 95% confidence interval is 0.0338. There are 60 homozygotes in gnomad4. There are 1709 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3565 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.4753-9C>T		intron_variant	Intron 34 of 42	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.4654-9C>T		intron_variant	Intron 33 of 41		NP_001070654.1
MYH14	NM_024729.4	c.4630-9C>T		intron_variant	Intron 32 of 40		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.4753-9C>T		intron_variant	Intron 34 of 42		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3565 AN: 152168 Hom.: 60 Cov.: 31

Gnomad AFR AF: 0.00654

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0226

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.0296

GnomAD3 exomes AF: 0.0234 AC: 5345 AN: 228342 Hom.: 83 AF XY: 0.0237 AC XY: 2925 AN XY: 123624

Gnomad AFR exome AF: 0.00604

Gnomad AMR exome AF: 0.0223

Gnomad ASJ exome AF: 0.0277

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00522

Gnomad FIN exome AF: 0.0230

Gnomad NFE exome AF: 0.0342

Gnomad OTH exome AF: 0.0277

GnomAD4 exome AF: 0.0309 AC: 44690 AN: 1448090 Hom.: 737 Cov.: 32 AF XY: 0.0302 AC XY: 21705 AN XY: 718932

Gnomad4 AFR exome AF: 0.00510

Gnomad4 AMR exome AF: 0.0224

Gnomad4 ASJ exome AF: 0.0255

Gnomad4 EAS exome AF: 0.000102

Gnomad4 SAS exome AF: 0.00575

Gnomad4 FIN exome AF: 0.0258

Gnomad4 NFE exome AF: 0.0355

Gnomad4 OTH exome AF: 0.0284

GnomAD4 genome AF: 0.0234 AC: 3565 AN: 152286 Hom.: 60 Cov.: 31 AF XY: 0.0230 AC XY: 1709 AN XY: 74462

Gnomad4 AFR AF: 0.00652

Gnomad4 AMR AF: 0.0318

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.0226

Gnomad4 NFE AF: 0.0349

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0267 Hom.: 30

Bravo AF: 0.0235

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Oct 13, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

4753-9C>T in Intron 34 of MYH14: This variant is not expected to have clinical s ignificance because it has been identified in 3.5% (244/6890) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs45591233). -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 07, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 4A Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00047
dbscSNV1_RF	Benign	0.25
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

Publications

LitVar

Other links and lift over

dbSNP: rs45591233; hg19: chr19-50792684;