rs2038761

Variant names:

• chr6-2680533-C-T
• rs2038761
• NM_001012418.5:c.688-242G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MYLK4	NM_001012418.5	c.688-242G>A		intron_variant	Intron 7 of 12	ENST00000274643.9	NP_001012418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK4	ENST00000274643.9	c.688-242G>A		intron_variant	Intron 7 of 12	1	NM_001012418.5	ENSP00000274643.7
MYLK4	ENST00000698900.1	n.967G>A		non_coding_transcript_exon_variant	Exon 9 of 9
MYLK4	ENST00000698899.1	c.856-242G>A		intron_variant	Intron 7 of 12			ENSP00000514016.1
MYLK4	ENST00000647417.1	c.670-242G>A		intron_variant	Intron 6 of 11			ENSP00000494309.1

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

African (AFR) AF: 0.0840 AC: 1326 AN: 15786

American (AMR) AF: 0.372 AC: 366 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1720 AN: 5152

East Asian (EAS) AF: 0.437 AC: 1588 AN: 3630

South Asian (SAS) AF: 0.327 AC: 5376 AN: 16458

European-Finnish (FIN) AF: 0.348 AC: 96 AN: 276

Middle Eastern (MID) AF: 0.305 AC: 494 AN: 1620

European-Non Finnish (NFE) AF: 0.288 AC: 219242 AN: 761850

Other (OTH) AF: 0.293 AC: 8008 AN: 27294

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

African (AFR) AF: 0.106 AC: 4393 AN: 41528

American (AMR) AF: 0.365 AC: 5573 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1088 AN: 3472

East Asian (EAS) AF: 0.445 AC: 2303 AN: 5174

South Asian (SAS) AF: 0.339 AC: 1635 AN: 4822

European-Finnish (FIN) AF: 0.330 AC: 3478 AN: 10538

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20257 AN: 67982

Other (OTH) AF: 0.295 AC: 623 AN: 2114

Alfa AF: 0.287 Hom.: 27922

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
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2038761; hg19: chr6-2680767;