rs4714261

Positions:

• chr6-39571431-C-T

Variant summary

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

The NM_145027.6(KIF6):​c.1181+6625G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,052 control chromosomes in the GnomAD database, including 5,830 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 0.25 (5830 hom., cov: 32)
• Consequence: KIF6 NM_145027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF6	NM_145027.6	c.1181+6625G>A		intron_variant		ENST00000287152.12	NP_659464.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF6	ENST00000287152.12	c.1181+6625G>A		intron_variant		2	NM_145027.6	ENSP00000287152	P1
KIF6	ENST00000458470.5	c.856+6625G>A		intron_variant		1		ENSP00000409417
KIF6	ENST00000538893.5	c.-299+6625G>A		intron_variant		5		ENSP00000441435

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37904 AN: 151934 Hom.: 5829 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0851

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.250 AC: 37939 AN: 152052 Hom.: 5830 Cov.: 32 AF XY: 0.253 AC XY: 18798 AN XY: 74332

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0849

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.249

Alfa AF: 0.182 Hom.: 4516

Bravo AF: 0.263

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
DANN	Benign	0.67

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: rs4714261; hg19: chr6-39539207;