NM_145027.6:c.2428+2743T>C

Variant names:

• chr6-39340966-A-G
• rs9471077
• NM_145027.6:c.2428+2743T>C

Variant summary

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

The NM_145027.6(KIF6):​c.2428+2743T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,926 control chromosomes in the GnomAD database, including 21,684 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 0.50 (21684 hom., cov: 32)
• Consequence: KIF6 NM_145027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 9 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]

LOC105375047 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 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.2428+2743T>C		intron	N/A	NP_659464.3
	KIF6	NM_001289020.3		c.2377+2743T>C		intron	N/A	NP_001275949.1
	KIF6	NM_001289021.3		c.2260+2743T>C		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.2428+2743T>C		intron	N/A	ENSP00000287152.7
	KIF6	ENST00000458470.5	TSL:1	c.2050+2743T>C		intron	N/A	ENSP00000409417.1
	KIF6	ENST00000229913.9	TSL:1	c.781+2743T>C		intron	N/A	ENSP00000229913.5

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76474 AN: 151808 Hom.: 21665 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.504 AC: 76544 AN: 151926 Hom.: 21684 Cov.: 32 AF XY: 0.499 AC XY: 37036 AN XY: 74240

African (AFR) AF: 0.779 AC: 32287 AN: 41452

American (AMR) AF: 0.391 AC: 5970 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1279 AN: 3472

East Asian (EAS) AF: 0.594 AC: 3051 AN: 5134

South Asian (SAS) AF: 0.477 AC: 2290 AN: 4804

European-Finnish (FIN) AF: 0.347 AC: 3662 AN: 10542

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.390 AC: 26502 AN: 67940

Other (OTH) AF: 0.493 AC: 1041 AN: 2110

Alfa AF: 0.448 Hom.: 24634

Bravo AF: 0.517

Asia WGS AF: 0.583 AC: 2027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.096
DANN	Benign	0.44
PhyloP100		-1.4
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: rs9471077; hg19: chr6-39308742;