1-200553141-G-A

Position:

• chr1-200553141-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014875.3(KIF14):​c.*247C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 237,336 control chromosomes in the GnomAD database, including 30,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (19626 hom., cov: 30)
  • Exomes 𝑓: 0.50 (11022 hom.)
• Consequence: KIF14 NM_014875.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.82

Genes affected

KIF14 (HGNC:19181): (kinesin family member 14) This gene encodes a member of the kinesin-3 superfamily of microtubule motor proteins. These proteins are involved in numerous processes including vesicle transport, chromosome segregation, mitotic spindle formation, and cytokinesis. In human HeLa-S3 and 293T cells, this protein is localized to the cytoplasm during interphase, to the spindle poles and spindle microtubules during mitosis, and to the midbody during cytokinesis. An internal motor domain displays microtubule-dependent ATPase activity, consistent with its function as a microtubule motor protein. Knockdown of this gene results in failed cytokinesis with endoreplication, which results in multinucleated cells. This gene has been identified as a likely oncogene in breast, lung and ovarian cancers, as well as retinoblastomas and gliomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 1-200553141-G-A is Benign according to our data. Variant chr1-200553141-G-A is described in ClinVar as [Benign]. Clinvar id is 1283604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF14	NM_014875.3	c.*247C>T		3_prime_UTR_variant	30/30	ENST00000367350.5	NP_055690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF14	ENST00000367350.5	c.*247C>T		3_prime_UTR_variant	30/30	2	NM_014875.3	ENSP00000356319	P1
KIF14	ENST00000614960.4	c.*247C>T		3_prime_UTR_variant	29/29	1		ENSP00000483069	P1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76772 AN: 151560 Hom.: 19632 Cov.: 30

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.500 AC: 42847 AN: 85660 Hom.: 11022 Cov.: 3 AF XY: 0.504 AC XY: 22389 AN XY: 44444

Gnomad4 AFR exome AF: 0.477

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.582

Gnomad4 EAS exome AF: 0.627

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.498

GnomAD4 genome AF: 0.506 AC: 76804 AN: 151676 Hom.: 19626 Cov.: 30 AF XY: 0.506 AC XY: 37521 AN XY: 74084

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.539

Alfa AF: 0.468 Hom.: 2036

Bravo AF: 0.510

Asia WGS AF: 0.576 AC: 2001 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.047
DANN	Benign	0.62

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: rs6667775; hg19: chr1-200522269; COSMIC: COSV66260624;