rs648691

Positions:

• chr19-50189839-T-C
• chr19-50189839-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000598205.5(MYH14):​c.-4+1532T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,052 control chromosomes in the GnomAD database, including 12,019 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 0.39 (12019 hom., cov: 32)
• Consequence: MYH14 ENST00000598205.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

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]

LOC124904746 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124904746	XR_007067298.1	n.165-10466A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000598205.5	c.-4+1532T>C		intron_variant		5		ENSP00000472543.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59779 AN: 151932 Hom.: 12006 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.393 AC: 59828 AN: 152052 Hom.: 12019 Cov.: 32 AF XY: 0.393 AC XY: 29237 AN XY: 74342

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.386

Alfa AF: 0.414 Hom.: 6232

Bravo AF: 0.384

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.50
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs648691; hg19: chr19-50693096;