chr1-170074763-G-C

Position:

• chr1-170074763-G-C

Variant summary

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

The XM_024454186.2(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 XM_024454186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIFAP3	XM_024454186.2	c.77+10272C>G		intron_variant			XP_024309954.1
KIFAP3	XM_047449531.1	c.77+10272C>G		intron_variant			XP_047305487.1
KIFAP3	XM_047449537.1	c.77+10272C>G		intron_variant			XP_047305493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIFAP3	ENST00000490550.1	n.174+10272C>G		intron_variant		5		ENSP00000518914.1
KIFAP3	ENST00000538366.5	c.-694C>G		upstream_gene_variant		2		ENSP00000444622.1

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

Gnomad4 AFR exome AF: 0.823

Gnomad4 AMR exome AF: 0.832

Gnomad4 ASJ exome AF: 0.743

Gnomad4 EAS exome AF: 0.996

Gnomad4 SAS exome AF: 0.836

Gnomad4 FIN exome AF: 0.738

Gnomad4 NFE exome AF: 0.699

Gnomad4 OTH exome AF: 0.750

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

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.768

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs522444; hg19: chr1-170043904;