17-29129237-G-C

Variant names:

• chr17-29129237-G-C
• rs11080078
• NM_078471.4:c.1000-6984C>G

Variant summary

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

The NM_078471.4(MYO18A):​c.1000-6984C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 371,892 control chromosomes in the GnomAD database, including 38,152 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 0.45 (16075 hom., cov: 32)
  • Exomes 𝑓: 0.45 (22077 hom.)
• Consequence: MYO18A NM_078471.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 3 publications found

Genes affected

MYO18A (HGNC:31104): (myosin XVIIIA) The protein encoded by this gene can bind GOLPH3, linking the Golgi to the cytoskeleton and influencing Golgi membrane trafficking. The encoded protein is also part of a complex that assembles lamellar actomyosin bundles and may be required for cell migration. [provided by RefSeq, Oct 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18A	NM_078471.4	c.1000-6984C>G		intron_variant	Intron 2 of 41	ENST00000527372.7	NP_510880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18A	ENST00000527372.7	c.1000-6984C>G		intron_variant	Intron 2 of 41	1	NM_078471.4	ENSP00000437073.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68803 AN: 151846 Hom.: 16068 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.466

GnomAD4 exome AF: 0.445 AC: 97873 AN: 219928 Hom.: 22077 AF XY: 0.446 AC XY: 46775 AN XY: 104956

African (AFR) AF: 0.417 AC: 1743 AN: 4176

American (AMR) AF: 0.406 AC: 103 AN: 254

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 772 AN: 1368

East Asian (EAS) AF: 0.855 AC: 776 AN: 908

South Asian (SAS) AF: 0.471 AC: 2102 AN: 4462

European-Finnish (FIN) AF: 0.574 AC: 39 AN: 68

Middle Eastern (MID) AF: 0.473 AC: 212 AN: 448

European-Non Finnish (NFE) AF: 0.441 AC: 88671 AN: 201020

Other (OTH) AF: 0.478 AC: 3455 AN: 7224

GnomAD4 genome AF: 0.453 AC: 68852 AN: 151964 Hom.: 16075 Cov.: 32 AF XY: 0.452 AC XY: 33569 AN XY: 74276

African (AFR) AF: 0.419 AC: 17358 AN: 41428

American (AMR) AF: 0.413 AC: 6301 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3472

East Asian (EAS) AF: 0.851 AC: 4388 AN: 5154

South Asian (SAS) AF: 0.510 AC: 2450 AN: 4808

European-Finnish (FIN) AF: 0.424 AC: 4481 AN: 10560

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30333 AN: 67954

Other (OTH) AF: 0.470 AC: 992 AN: 2110

Alfa AF: 0.285 Hom.: 674

Bravo AF: 0.452

Asia WGS AF: 0.640 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.59
DANN	Benign	0.60
PhyloP100		0.14
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: rs11080078; hg19: chr17-27456255;