rs11704382

Positions:

• chr22-36332107-C-A
• chr22-36332107-C-G

Variant summary

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

The NM_002473.6(MYH9):​c.491-4619G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 152,140 control chromosomes in the GnomAD database, including 256 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 0.049 (256 hom., cov: 32)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.491-4619G>T		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.491-4619G>T		intron_variant		1	NM_002473.6	P1

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7488 AN: 152022 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0349

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.0851

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0897

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.0532

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

GnomAD4 genome AF: 0.0492 AC: 7486 AN: 152140 Hom.: 256 Cov.: 32 AF XY: 0.0501 AC XY: 3723 AN XY: 74362

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.0351

Gnomad4 ASJ AF: 0.0539

Gnomad4 EAS AF: 0.0847

Gnomad4 SAS AF: 0.0541

Gnomad4 FIN AF: 0.0897

Gnomad4 NFE AF: 0.0666

Gnomad4 OTH AF: 0.0536

Alfa AF: 0.0608 Hom.: 287

Bravo AF: 0.0432

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11704382; hg19: chr22-36728152;