NM_004145.4:c.5386+67A>G

Variant names:

• chr19-17206443-A-G
• rs2279002
• NM_004145.4:c.5386+67A>G

Variant summary

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

The NM_004145.4(MYO9B):​c.5386+67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,565,702 control chromosomes in the GnomAD database, including 106,512 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 0.39 (12572 hom., cov: 33)
  • Exomes 𝑓: 0.35 (93940 hom.)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004145.4. 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
	MYO9B	NM_004145.4	MANE Select	c.5386+67A>G		intron	N/A	NP_004136.2
	MYO9B	NM_001130065.2		c.5386+67A>G		intron	N/A	NP_001123537.1	Q13459-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9B	ENST00000682292.1	MANE Select	c.5386+67A>G		intron	N/A	ENSP00000507803.1	Q13459-1
	MYO9B	ENST00000595618.5	TSL:1	c.5386+67A>G		intron	N/A	ENSP00000471457.1	Q13459-2
	MYO9B	ENST00000593533.1	TSL:1	n.829-236A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59597 AN: 152022 Hom.: 12561 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.351 AC: 495986 AN: 1413562 Hom.: 93940 AF XY: 0.352 AC XY: 245895 AN XY: 699442

African (AFR) AF: 0.447 AC: 14682 AN: 32878

American (AMR) AF: 0.646 AC: 26605 AN: 41162

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 4993 AN: 24174

East Asian (EAS) AF: 0.757 AC: 29429 AN: 38876

South Asian (SAS) AF: 0.434 AC: 34985 AN: 80584

European-Finnish (FIN) AF: 0.357 AC: 14111 AN: 39578

Middle Eastern (MID) AF: 0.317 AC: 1717 AN: 5424

European-Non Finnish (NFE) AF: 0.319 AC: 348258 AN: 1092200

Other (OTH) AF: 0.361 AC: 21206 AN: 58686

GnomAD4 genome AF: 0.392 AC: 59625 AN: 152140 Hom.: 12572 Cov.: 33 AF XY: 0.398 AC XY: 29603 AN XY: 74370

African (AFR) AF: 0.438 AC: 18173 AN: 41514

American (AMR) AF: 0.515 AC: 7870 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3472

East Asian (EAS) AF: 0.762 AC: 3927 AN: 5152

South Asian (SAS) AF: 0.457 AC: 2206 AN: 4828

European-Finnish (FIN) AF: 0.377 AC: 3990 AN: 10572

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21558 AN: 67994

Other (OTH) AF: 0.392 AC: 828 AN: 2114

Alfa AF: 0.256 Hom.: 1174

Bravo AF: 0.410

Asia WGS AF: 0.559 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.11
DANN	Benign	0.50
PhyloP100		-0.68
PromoterAI		0.0011	Neutral
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: rs2279002; hg19: chr19-17317252;