19-17172493-T-C

Variant names:

• chr19-17172493-T-C
• rs2279008
• NM_004145.4:c.1935+16T>C

Variant summary

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

The NM_004145.4(MYO9B):​c.1935+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,610,968 control chromosomes in the GnomAD database, including 52,018 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 0.23 (4430 hom., cov: 31)
  • Exomes 𝑓: 0.25 (47588 hom.)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 49 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9B	NM_004145.4	MANE Select	c.1935+16T>C		intron	N/A	NP_004136.2
	MYO9B	NM_001130065.2		c.1935+16T>C		intron	N/A	NP_001123537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9B	ENST00000682292.1	MANE Select	c.1935+16T>C		intron	N/A	ENSP00000507803.1
	MYO9B	ENST00000595618.5	TSL:1	c.1935+16T>C		intron	N/A	ENSP00000471457.1
	MYO9B	ENST00000594824.5	TSL:5	c.1935+16T>C		intron	N/A	ENSP00000471367.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34690 AN: 151918 Hom.: 4428 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.254

GnomAD2 exomes AF: 0.252 AC: 61403 AN: 243994 AF XY: 0.250

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.353

Gnomad FIN exome AF: 0.365

Gnomad NFE exome AF: 0.248

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.252 AC: 367765 AN: 1458932 Hom.: 47588 Cov.: 35 AF XY: 0.251 AC XY: 182256 AN XY: 725486

African (AFR) AF: 0.115 AC: 3843 AN: 33446

American (AMR) AF: 0.255 AC: 11298 AN: 44238

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5382 AN: 26018

East Asian (EAS) AF: 0.345 AC: 13684 AN: 39640

South Asian (SAS) AF: 0.213 AC: 18261 AN: 85822

European-Finnish (FIN) AF: 0.356 AC: 18895 AN: 53096

Middle Eastern (MID) AF: 0.242 AC: 1388 AN: 5744

European-Non Finnish (NFE) AF: 0.252 AC: 280055 AN: 1110648

Other (OTH) AF: 0.248 AC: 14959 AN: 60280

GnomAD4 genome AF: 0.228 AC: 34707 AN: 152036 Hom.: 4430 Cov.: 31 AF XY: 0.235 AC XY: 17495 AN XY: 74304

African (AFR) AF: 0.124 AC: 5130 AN: 41504

American (AMR) AF: 0.261 AC: 3988 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3468

East Asian (EAS) AF: 0.354 AC: 1825 AN: 5150

South Asian (SAS) AF: 0.212 AC: 1022 AN: 4820

European-Finnish (FIN) AF: 0.376 AC: 3978 AN: 10568

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17250 AN: 67952

Other (OTH) AF: 0.254 AC: 537 AN: 2114

Alfa AF: 0.242 Hom.: 19850

Bravo AF: 0.217

Asia WGS AF: 0.251 AC: 875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.35
PhyloP100		-0.25
PromoterAI		-0.0027	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: rs2279008; hg19: chr19-17283303; COSMIC: COSV68278914; COSMIC: COSV68278914;