rs2038761

Positions:

• chr6-2680533-C-T

Variant summary

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

The NM_001012418.5(MYLK4):​c.688-242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 985,164 control chromosomes in the GnomAD database, including 40,468 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 0.26 (6040 hom., cov: 32)
  • Exomes 𝑓: 0.29 (34428 hom.)
• Consequence: MYLK4 NM_001012418.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

Genes affected

MYLK4 (HGNC:27972): (myosin light chain kinase family member 4) Predicted to enable myosin light chain kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLK4	NM_001012418.5	c.688-242G>A		intron_variant		ENST00000274643.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK4	ENST00000274643.9	c.688-242G>A		intron_variant		1	NM_001012418.5	A2
MYLK4	ENST00000647417.1	c.670-242G>A		intron_variant				P2
MYLK4	ENST00000698899.1	c.856-242G>A		intron_variant				A2
MYLK4	ENST00000698900.1	n.967G>A		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39566 AN: 151996 Hom.: 6040 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.292

GnomAD4 exome AF: 0.286 AC: 238216 AN: 833050 Hom.: 34428 Cov.: 29 AF XY: 0.286 AC XY: 109893 AN XY: 384686

Gnomad4 AFR exome AF: 0.0840

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.437

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.260 AC: 39569 AN: 152114 Hom.: 6040 Cov.: 32 AF XY: 0.267 AC XY: 19857 AN XY: 74338

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.295

Alfa AF: 0.295 Hom.: 14203

Bravo AF: 0.255

Asia WGS AF: 0.326 AC: 1133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.5
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2038761; hg19: chr6-2680767;