rs2750014

Positions:

• chr1-169933936-C-T

Variant summary

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

The NM_014970.4(KIFAP3):​c.2274-12155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,032 control chromosomes in the GnomAD database, including 4,440 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 0.21 (4440 hom., cov: 32)
• Consequence: KIFAP3 NM_014970.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

Genes affected

KIFAP3 (HGNC:17060): (kinesin associated protein 3) The small G protein GDP dissociation stimulator (smg GDS) is a regulator protein having two activities on a group of small G proteins including the Rho and Rap1 family members and Ki-Ras; one is to stimulate their GDP/GTP exchange reactions, and the other is to inhibit their interactions with membranes. The protein encoded by this gene contains 9 'Armadillo' repeats and interacts with the smg GDS protein through these repeats. This protein, which is highly concentrated around the endoplasmic reticulum, is phosphorylated by v-src, and this phosphorylation reduces the affinity of the protein for smg GDS. It is thought that this protein serves as a linker between human chromosome-associated polypeptide (HCAP) and KIF3A/B, a kinesin superfamily protein in the nucleus, and that it plays a role in the interaction of chromosomes with an ATPase motor protein. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIFAP3	NM_014970.4	c.2274-12155G>A		intron_variant		ENST00000361580.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIFAP3	ENST00000361580.7	c.2274-12155G>A		intron_variant		1	NM_014970.4	P1
KIFAP3	ENST00000367767.5	c.2142-12155G>A		intron_variant		1
KIFAP3	ENST00000367765.5	c.2154-12155G>A		intron_variant		2
KIFAP3	ENST00000538366.5	c.2040-12155G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32490 AN: 151914 Hom.: 4439 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.214 AC: 32496 AN: 152032 Hom.: 4440 Cov.: 32 AF XY: 0.219 AC XY: 16279 AN XY: 74306

Gnomad4 AFR AF: 0.0502

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.222

Alfa AF: 0.244 Hom.: 2511

Bravo AF: 0.204

Asia WGS AF: 0.317 AC: 1102 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.41

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: rs2750014; hg19: chr1-169903077;