rs6505114

Positions:

• chr17-29172122-G-A
• chr17-29172122-G-C

Variant summary

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

The NM_078471.4(MYO18A):​c.-81-5101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,022 control chromosomes in the GnomAD database, including 31,816 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 0.64 (31816 hom., cov: 32)
• Consequence: MYO18A NM_078471.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO18A	NM_078471.4	c.-81-5101C>T		intron_variant		ENST00000527372.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO18A	ENST00000527372.7	c.-81-5101C>T		intron_variant		1	NM_078471.4	A1
MYO18A	ENST00000533112.5	c.-82+4450C>T		intron_variant		1
MYO18A	ENST00000531253.5	c.-81-5101C>T		intron_variant		5		A1
MYO18A	ENST00000704659.1	c.-81-5101C>T		intron_variant				P3

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96437 AN: 151904 Hom.: 31780 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.635 AC: 96538 AN: 152022 Hom.: 31816 Cov.: 32 AF XY: 0.636 AC XY: 47214 AN XY: 74294

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.622

Alfa AF: 0.562 Hom.: 49750

Bravo AF: 0.638

Asia WGS AF: 0.783 AC: 2721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.66

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: rs6505114; hg19: chr17-27499140;