rs11673417

chr19-17159689-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004145.4(MYO9B):c.1419+205C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 152,334 control chromosomes in the GnomAD database, including 34 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 0.018 (34 hom., cov: 32)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.723

Genes affected

MYO9B (HGNC:7609): (myosin IXB) This gene encodes a member of the myosin family of actin-based molecular motor heavy chain proteins. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-9 (MYH9). The protein has four IQ motifs located in the neck domain that bind calmodulin, which serves as a light chain. The protein complex has a single-headed structure and exhibits processive movement on actin filaments toward the minus-end. The protein also has rho-GTPase activity. Polymorphisms in this gene are associated with celiac disease and ulcerative colitis susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0183 (2795/152334) while in subpopulation NFE AF= 0.0226 (1535/68026). AF 95% confidence interval is 0.0216. There are 34 homozygotes in gnomad4. There are 1440 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 2797 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO9B	NM_004145.4	c.1419+205C>G		intron_variant		ENST00000682292.1
MYO9B	NM_001130065.2	c.1419+205C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO9B	ENST00000682292.1	c.1419+205C>G		intron_variant			NM_004145.4	A2
	ENST00000597216.5	n.128-1977G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2797 AN: 152216 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.00410

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0613

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0430

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.0201

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

GnomAD4 genome AF: 0.0183 AC: 2795 AN: 152334 Hom.: 34 Cov.: 32 AF XY: 0.0193 AC XY: 1440 AN XY: 74490

Gnomad4 AFR AF: 0.00409

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0613

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0182

Gnomad4 FIN AF: 0.0430

Gnomad4 NFE AF: 0.0226

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.0214 Hom.: 8

Bravo AF: 0.0159

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.5
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11673417; hg19: chr19-17270499;