chr6-39381025-C-A

Variant names:

• chr6-39381025-C-A
• rs9394587
• NM_145027.6:c.1861+4597G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145027.6(KIF6):​c.1861+4597G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,070 control chromosomes in the GnomAD database, including 14,440 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 0.41 (14440 hom., cov: 32)
• Consequence: KIF6 NM_145027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 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+4597G>T		intron	N/A	NP_659464.3
	KIF6	NM_001289020.3		c.1811-18507G>T		intron	N/A	NP_001275949.1
	KIF6	NM_001289021.3		c.1693+4597G>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+4597G>T		intron	N/A	ENSP00000287152.7
	KIF6	ENST00000458470.5	TSL:1	c.1534+4597G>T		intron	N/A	ENSP00000409417.1
	KIF6	ENST00000229913.9	TSL:1	c.214+4597G>T		intron	N/A	ENSP00000229913.5

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61790 AN: 151952 Hom.: 14438 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.406 AC: 61790 AN: 152070 Hom.: 14440 Cov.: 32 AF XY: 0.410 AC XY: 30439 AN XY: 74330

African (AFR) AF: 0.157 AC: 6504 AN: 41512

American (AMR) AF: 0.522 AC: 7972 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1482 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2945 AN: 5178

South Asian (SAS) AF: 0.343 AC: 1652 AN: 4814

European-Finnish (FIN) AF: 0.553 AC: 5839 AN: 10550

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34051 AN: 67950

Other (OTH) AF: 0.402 AC: 849 AN: 2110

Alfa AF: 0.464 Hom.: 28508

Bravo AF: 0.395

Asia WGS AF: 0.426 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.89
DANN	Benign	0.73
PhyloP100		-0.62
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: rs9394587; hg19: chr6-39348801;