NM_145027.6:c.2181-1490G>T

Variant names:

• chr6-39348016-C-A
• rs9462535
• NM_145027.6:c.2181-1490G>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.2181-1490G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,122 control chromosomes in the GnomAD database, including 21,412 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 (21412 hom., cov: 33)
• Consequence: KIF6 NM_145027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997
• Publications: 5 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 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.2181-1490G>T		intron	N/A	NP_659464.3
	KIF6	NM_001289020.3		c.2130-1490G>T		intron	N/A	NP_001275949.1
	KIF6	NM_001289021.3		c.2013-1490G>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.2181-1490G>T		intron	N/A	ENSP00000287152.7
	KIF6	ENST00000458470.5	TSL:1	c.1854-2227G>T		intron	N/A	ENSP00000409417.1
	KIF6	ENST00000229913.9	TSL:1	c.534-1490G>T		intron	N/A	ENSP00000229913.5

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75949 AN: 152004 Hom.: 21389 Cov.: 33

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.500 AC: 76024 AN: 152122 Hom.: 21412 Cov.: 33 AF XY: 0.495 AC XY: 36777 AN XY: 74356

African (AFR) AF: 0.774 AC: 32130 AN: 41526

American (AMR) AF: 0.382 AC: 5840 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3468

East Asian (EAS) AF: 0.591 AC: 3050 AN: 5164

South Asian (SAS) AF: 0.477 AC: 2298 AN: 4816

European-Finnish (FIN) AF: 0.345 AC: 3651 AN: 10586

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26282 AN: 67960

Other (OTH) AF: 0.490 AC: 1035 AN: 2114

Alfa AF: 0.435 Hom.: 25795

Bravo AF: 0.513

Asia WGS AF: 0.588 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.22
DANN	Benign	0.74
PhyloP100		-1.0
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: rs9462535; hg19: chr6-39315792;