rs7246865

Positions:

• chr19-17108295-G-A

Variant summary

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

The NM_004145.4(MYO9B):​c.840+5738G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,052 control chromosomes in the GnomAD database, including 10,684 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 0.36 (10684 hom., cov: 32)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.840+5738G>A		intron_variant		ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.840+5738G>A		intron_variant			NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.840+5738G>A		intron_variant			NM_004145.4	ENSP00000507803	A2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54165 AN: 151934 Hom.: 10663 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.357 AC: 54241 AN: 152052 Hom.: 10684 Cov.: 32 AF XY: 0.360 AC XY: 26723 AN XY: 74326

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.376

Alfa AF: 0.301 Hom.: 9544

Bravo AF: 0.379

Asia WGS AF: 0.402 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.7
DANN	Benign	0.94

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: rs7246865; hg19: chr19-17219105;