rs4820230

Positions:

• chr22-36313494-G-A
• chr22-36313494-G-T

Variant summary

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

The ENST00000216181.11(MYH9):​c.1554+651C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 147,572 control chromosomes in the GnomAD database, including 23,805 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 0.54 (23805 hom., cov: 25)
• Consequence: MYH9 ENST00000216181.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

Genes affected

MYH9 (HGNC:7579): (myosin heavy chain 9) This gene encodes a conventional non-muscle myosin; this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B). The encoded protein is a myosin IIA heavy chain that contains an IQ domain and a myosin head-like domain which is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape. Defects in this gene have been associated with non-syndromic sensorineural deafness autosomal dominant type 17, Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6	c.1554+651C>T		intron_variant		ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.1554+651C>T		intron_variant		1	NM_002473.6	ENSP00000216181	P1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 80222 AN: 147486 Hom.: 23806 Cov.: 25

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.544 AC: 80236 AN: 147572 Hom.: 23805 Cov.: 25 AF XY: 0.537 AC XY: 38376 AN XY: 71428

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.559

Alfa AF: 0.644 Hom.: 42139

Bravo AF: 0.538

Asia WGS AF: 0.259 AC: 901 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs4820230; hg19: chr22-36709539;