rs4801824

Variant names:

• chr19-50253873-T-C
• rs4801824
• NM_001145809.2:c.1945+1120T>C

Variant summary

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

The NM_001145809.2(MYH14):​c.1945+1120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,036 control chromosomes in the GnomAD database, including 6,334 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 0.28 (6334 hom., cov: 32)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 4 publications found

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]

MYH14 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 4A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145809.2. 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
	MYH14	NM_001145809.2	MANE Select	c.1945+1120T>C		intron	N/A	NP_001139281.1	Q7Z406-2
	MYH14	NM_001077186.2		c.1945+1120T>C		intron	N/A	NP_001070654.1	Q7Z406-6
	MYH14	NM_024729.4		c.1921+1120T>C		intron	N/A	NP_079005.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	ENST00000642316.2	MANE Select	c.1945+1120T>C		intron	N/A	ENSP00000493594.1	Q7Z406-2
	MYH14	ENST00000599920.5	TSL:1	c.1945+1120T>C		intron	N/A	ENSP00000469573.1	M0QY43
	MYH14	ENST00000425460.6	TSL:5	c.1945+1120T>C		intron	N/A	ENSP00000407879.1	Q7Z406-6

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43269 AN: 151918 Hom.: 6320 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.285 AC: 43315 AN: 152036 Hom.: 6334 Cov.: 32 AF XY: 0.286 AC XY: 21265 AN XY: 74304

African (AFR) AF: 0.240 AC: 9946 AN: 41482

American (AMR) AF: 0.227 AC: 3470 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1334 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1582 AN: 5158

South Asian (SAS) AF: 0.299 AC: 1435 AN: 4804

European-Finnish (FIN) AF: 0.369 AC: 3900 AN: 10566

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20829 AN: 67974

Other (OTH) AF: 0.282 AC: 597 AN: 2114

Alfa AF: 0.297 Hom.: 12609

Bravo AF: 0.274

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.45
PhyloP100		-0.28
Mutation Taster		=100/0	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: rs4801824; hg19: chr19-50757130;