6-39549714-G-C

Position:

• chr6-39549714-G-C

Variant summary

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

The NM_145027.6(KIF6):​c.1182-4026C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,034 control chromosomes in the GnomAD database, including 5,742 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 0.24 (5742 hom., cov: 32)
• Consequence: KIF6 NM_145027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF6	NM_145027.6	c.1182-4026C>G		intron_variant		ENST00000287152.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF6	ENST00000287152.12	c.1182-4026C>G		intron_variant		2	NM_145027.6	P1
KIF6	ENST00000458470.5	c.857-4026C>G		intron_variant		1
KIF6	ENST00000538893.5	c.-298-4026C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37047 AN: 151916 Hom.: 5735 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0396

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.244 AC: 37095 AN: 152034 Hom.: 5742 Cov.: 32 AF XY: 0.247 AC XY: 18355 AN XY: 74336

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.0397

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.229

Alfa AF: 0.0841 Hom.: 103

Bravo AF: 0.256

Asia WGS AF: 0.202 AC: 702 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	2.3
DANN	Benign	0.53

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: rs11752175; hg19: chr6-39517490;