chr1-170026661-C-T

Variant names:

• chr1-170026661-C-T
• rs1541160
• NM_014970.4:c.842-2065G>A

Variant summary

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

The NM_014970.4(KIFAP3):​c.842-2065G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,100 control chromosomes in the GnomAD database, including 44,687 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 0.76 (44687 hom., cov: 31)
• Consequence: KIFAP3 NM_014970.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.837
• Publications: 36 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014970.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFAP3	NM_014970.4	MANE Select	c.842-2065G>A		intron	N/A	NP_055785.2
	KIFAP3	NM_001375830.1		c.842-2065G>A		intron	N/A	NP_001362759.1
	KIFAP3	NM_001375831.1		c.842-2065G>A		intron	N/A	NP_001362760.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFAP3	ENST00000361580.7	TSL:1 MANE Select	c.842-2065G>A		intron	N/A	ENSP00000354560.2	Q92845-1
	KIFAP3	ENST00000367767.5	TSL:1	c.710-2065G>A		intron	N/A	ENSP00000356741.1	Q92845-2
	KIFAP3	ENST00000490550.2	TSL:5	c.887-2065G>A		intron	N/A	ENSP00000518914.1	A0AAQ5BGI3

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115886 AN: 151982 Hom.: 44618 Cov.: 31

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.763 AC: 116012 AN: 152100 Hom.: 44687 Cov.: 31 AF XY: 0.767 AC XY: 57039 AN XY: 74336

African (AFR) AF: 0.815 AC: 33807 AN: 41496

American (AMR) AF: 0.802 AC: 12266 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2576 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5134 AN: 5166

South Asian (SAS) AF: 0.844 AC: 4067 AN: 4818

European-Finnish (FIN) AF: 0.741 AC: 7826 AN: 10558

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47818 AN: 67978

Other (OTH) AF: 0.767 AC: 1623 AN: 2116

Alfa AF: 0.731 Hom.: 144171

Bravo AF: 0.771

Asia WGS AF: 0.935 AC: 3250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.81
DANN	Benign	0.24
PhyloP100		-0.84
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: rs1541160; hg19: chr1-169995802;