chr6-39381754-G-A

Variant names:

• chr6-39381754-G-A
• rs721755
• NM_145027.6:c.1861+3868C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_145027.6(KIF6):​c.1861+3868C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 152,132 control chromosomes in the GnomAD database, including 51,152 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 0.81 (51152 hom., cov: 32)
• Consequence: KIF6 NM_145027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 3 publications found

Genes affected

KIF6 (HGNC:21202): (kinesin family member 6) This gene encodes a member of a family of molecular motors which are involved in intracellular transport of protein complexes, membrane organelles, and messenger ribonucleic acid along microtubules. Kinesins function as homodimeric molecules with two N-terminal head domains that move along microtubules and two C-terminal tail domains that interact with the transported cargo, either directly or indirectly, through adapter molecules. This gene is ubiquitously expressed in coronary arteries and other vascular tissue. A naturally occurring mutation in this gene is associated with coronary heart disease. [provided by RefSeq, May 2017]

LOC107986594 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145027.6. 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
	KIF6	NM_145027.6	MANE Select	c.1861+3868C>T		intron	N/A	NP_659464.3
	KIF6	NM_001289020.3		c.1811-19236C>T		intron	N/A	NP_001275949.1
	KIF6	NM_001289021.3		c.1693+3868C>T		intron	N/A	NP_001275950.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF6	ENST00000287152.12	TSL:2 MANE Select	c.1861+3868C>T		intron	N/A	ENSP00000287152.7
	KIF6	ENST00000458470.5	TSL:1	c.1534+3868C>T		intron	N/A	ENSP00000409417.1
	KIF6	ENST00000229913.9	TSL:1	c.214+3868C>T		intron	N/A	ENSP00000229913.5

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123821 AN: 152014 Hom.: 51094 Cov.: 32

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.793

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

GnomAD4 genome AF: 0.815 AC: 123932 AN: 152132 Hom.: 51152 Cov.: 32 AF XY: 0.813 AC XY: 60439 AN XY: 74380

African (AFR) AF: 0.959 AC: 39835 AN: 41530

American (AMR) AF: 0.802 AC: 12262 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2591 AN: 3468

East Asian (EAS) AF: 0.661 AC: 3417 AN: 5170

South Asian (SAS) AF: 0.685 AC: 3296 AN: 4810

European-Finnish (FIN) AF: 0.796 AC: 8420 AN: 10574

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51477 AN: 67974

Other (OTH) AF: 0.787 AC: 1664 AN: 2114

Alfa AF: 0.768 Hom.: 81915

Bravo AF: 0.820

Asia WGS AF: 0.746 AC: 2591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.79
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs721755; hg19: chr6-39349530;