rs4820230

Variant names:

• chr22-36313494-G-A
• rs4820230
• NM_002473.6:c.1554+651C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_002473.6(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 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 6 publications found

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]

MYH9 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 17

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
• May-Hegglin anomaly

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002473.6. 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
	MYH9	NM_002473.6	MANE Select	c.1554+651C>T		intron	N/A	NP_002464.1	P35579-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	ENST00000216181.11	TSL:1 MANE Select	c.1554+651C>T		intron	N/A	ENSP00000216181.6	P35579-1
	MYH9	ENST00000685801.1		c.1554+651C>T		intron	N/A	ENSP00000510688.1	A0A8I5KWT8
	MYH9	ENST00000955568.1		c.1554+651C>T		intron	N/A	ENSP00000625627.1

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

African (AFR) AF: 0.330 AC: 13214 AN: 40068

American (AMR) AF: 0.613 AC: 8979 AN: 14642

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1825 AN: 3456

East Asian (EAS) AF: 0.218 AC: 1098 AN: 5046

South Asian (SAS) AF: 0.385 AC: 1826 AN: 4740

European-Finnish (FIN) AF: 0.643 AC: 5760 AN: 8958

Middle Eastern (MID) AF: 0.535 AC: 152 AN: 284

European-Non Finnish (NFE) AF: 0.676 AC: 45547 AN: 67420

Other (OTH) AF: 0.559 AC: 1151 AN: 2058

Alfa AF: 0.641 Hom.: 49998

Bravo AF: 0.538

Asia WGS AF: 0.259 AC: 901 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.80
PhyloP100		0.061
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4820230; hg19: chr22-36709539;