6-2715448-A-G

Variant names:

• chr6-2715448-A-G
• rs17291546
• NM_001012418.5:c.160-22589T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001012418.5(MYLK4):​c.160-22589T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 152,274 control chromosomes in the GnomAD database, including 66 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 0.024 (66 hom., cov: 32)
• Consequence: MYLK4 NM_001012418.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 3 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=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0242 (3692/152274) while in subpopulation NFE AF = 0.0354 (2406/68008). AF 95% confidence interval is 0.0342. There are 66 homozygotes in GnomAd4. There are 1650 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 66 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012418.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK4	NM_001012418.5	MANE Select	c.160-22589T>C		intron	N/A	NP_001012418.2
	MYLK4	NM_001347872.2		c.328-22589T>C		intron	N/A	NP_001334801.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK4	ENST00000274643.9	TSL:1 MANE Select	c.160-22589T>C		intron	N/A	ENSP00000274643.7
	MYLK4	ENST00000698899.1		c.328-22589T>C		intron	N/A	ENSP00000514016.1
	MYLK4	ENST00000647417.1		c.142-22589T>C		intron	N/A	ENSP00000494309.1

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3693 AN: 152156 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.00615

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0242 AC: 3692 AN: 152274 Hom.: 66 Cov.: 32 AF XY: 0.0222 AC XY: 1650 AN XY: 74456

African (AFR) AF: 0.00614 AC: 255 AN: 41552

American (AMR) AF: 0.0288 AC: 440 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00476 AC: 23 AN: 4828

European-Finnish (FIN) AF: 0.00386 AC: 41 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0354 AC: 2406 AN: 68008

Other (OTH) AF: 0.0364 AC: 77 AN: 2114

Alfa AF: 0.0319 Hom.: 12

Bravo AF: 0.0265

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.63
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

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: rs17291546; hg19: chr6-2715682;