chr6-2715448-A-G

Position:

• chr6-2715448-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 66 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYLK4	NM_001012418.5	c.160-22589T>C		intron_variant		ENST00000274643.9	NP_001012418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYLK4	ENST00000274643.9	c.160-22589T>C		intron_variant		1	NM_001012418.5	ENSP00000274643	A2
MYLK4	ENST00000647417.1	c.142-22589T>C		intron_variant				ENSP00000494309	P2
MYLK4	ENST00000698899.1	c.328-22589T>C		intron_variant				ENSP00000514016	A2
MYLK4	ENST00000698900.1	n.421-22589T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.00614

Gnomad4 AMR AF: 0.0288

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.0354

Gnomad4 OTH AF: 0.0364

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.63

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: rs17291546; hg19: chr6-2715682;