1-170074763-G-C

Variant names:

• chr1-170074763-G-C
• rs522444
• ENST00000490550.2:c.77+10272C>G

Variant summary

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

The ENST00000490550.2(KIFAP3):​c.77+10272C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,249,850 control chromosomes in the GnomAD database, including 330,385 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 (44680 hom., cov: 32)
  • Exomes 𝑓: 0.72 (285705 hom.)
• Consequence: KIFAP3 ENST00000490550.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 10 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000490550.2. 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
	KIFAP3	NM_014970.4	MANE Select	c.-296C>G		upstream_gene	N/A	NP_055785.2
	KIFAP3	NM_001375830.1		c.-296C>G		upstream_gene	N/A	NP_001362759.1
	KIFAP3	NM_001375831.1		c.-296C>G		upstream_gene	N/A	NP_001362760.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFAP3	ENST00000490550.2	TSL:5	c.77+10272C>G		intron	N/A	ENSP00000518914.1
	KIFAP3	ENST00000361580.7	TSL:1 MANE Select	c.-296C>G		upstream_gene	N/A	ENSP00000354560.2
	KIFAP3	ENST00000367767.5	TSL:1	c.-296C>G		upstream_gene	N/A	ENSP00000356741.1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115887 AN: 152042 Hom.: 44613 Cov.: 32

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.766

GnomAD4 exome AF: 0.719 AC: 788953 AN: 1097690 Hom.: 285705 Cov.: 30 AF XY: 0.719 AC XY: 376106 AN XY: 522794

African (AFR) AF: 0.823 AC: 20638 AN: 25076

American (AMR) AF: 0.832 AC: 12572 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 10264 AN: 13820

East Asian (EAS) AF: 0.996 AC: 23952 AN: 24054

South Asian (SAS) AF: 0.836 AC: 34342 AN: 41062

European-Finnish (FIN) AF: 0.738 AC: 12307 AN: 16682

Middle Eastern (MID) AF: 0.762 AC: 2163 AN: 2838

European-Non Finnish (NFE) AF: 0.699 AC: 640483 AN: 916050

Other (OTH) AF: 0.750 AC: 32232 AN: 43000

GnomAD4 genome AF: 0.762 AC: 116011 AN: 152160 Hom.: 44680 Cov.: 32 AF XY: 0.767 AC XY: 57050 AN XY: 74376

African (AFR) AF: 0.814 AC: 33804 AN: 41520

American (AMR) AF: 0.802 AC: 12267 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2582 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5123 AN: 5158

South Asian (SAS) AF: 0.845 AC: 4076 AN: 4822

European-Finnish (FIN) AF: 0.741 AC: 7845 AN: 10590

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47795 AN: 67982

Other (OTH) AF: 0.768 AC: 1623 AN: 2114

Alfa AF: 0.630 Hom.: 1754

Bravo AF: 0.771

Asia WGS AF: 0.933 AC: 3245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.62
PhyloP100		0.24
PromoterAI		-0.054	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs522444; hg19: chr1-170043904;