rs1476009

Variant names:

• chr22-36290010-A-G
• rs1476009
• NM_002473.6:c.4345-713T>C

Variant summary

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

The NM_002473.6(MYH9):​c.4345-713T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 152,230 control chromosomes in the GnomAD database, including 71,594 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 0.97 (71594 hom., cov: 31)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12
• Publications: 1 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: G2P, Labcorp Genetics (formerly Invitae)
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.4345-713T>C		intron_variant	Intron 31 of 40	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.4345-713T>C		intron_variant	Intron 31 of 40	1	NM_002473.6	ENSP00000216181.6
MYH9	ENST00000685801.1	c.4408-713T>C		intron_variant	Intron 32 of 41			ENSP00000510688.1
MYH9	ENST00000691109.1	n.4640-713T>C		intron_variant	Intron 25 of 34

Frequencies

GnomAD3 genomes AF: 0.970 AC: 147520 AN: 152112 Hom.: 71527 Cov.: 31

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.968

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

GnomAD4 genome AF: 0.970 AC: 147647 AN: 152230 Hom.: 71594 Cov.: 31 AF XY: 0.970 AC XY: 72189 AN XY: 74424

African (AFR) AF: 0.959 AC: 39817 AN: 41506

American (AMR) AF: 0.980 AC: 14994 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 3324 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5180 AN: 5184

South Asian (SAS) AF: 0.985 AC: 4753 AN: 4826

European-Finnish (FIN) AF: 0.963 AC: 10202 AN: 10596

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66146 AN: 68028

Other (OTH) AF: 0.969 AC: 2046 AN: 2112

Alfa AF: 0.972 Hom.: 22431

Bravo AF: 0.972

Asia WGS AF: 0.990 AC: 3442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.088
DANN	Benign	0.25
PhyloP100		-3.1
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: rs1476009; hg19: chr22-36686056;