rs648576

Variant names:

• chr1-169930286-C-T
• rs648576
• NM_014970.4:c.2274-8505G>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.2274-8505G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,990 control chromosomes in the GnomAD database, including 4,658 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 0.24 (4658 hom., cov: 32)
• Consequence: KIFAP3 NM_014970.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFAP3	NM_014970.4	c.2274-8505G>A		intron_variant	Intron 19 of 19	ENST00000361580.7	NP_055785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFAP3	ENST00000361580.7	c.2274-8505G>A		intron_variant	Intron 19 of 19	1	NM_014970.4	ENSP00000354560.2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36037 AN: 151872 Hom.: 4657 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.237 AC: 36032 AN: 151990 Hom.: 4658 Cov.: 32 AF XY: 0.233 AC XY: 17339 AN XY: 74266

African (AFR) AF: 0.185 AC: 7681 AN: 41442

American (AMR) AF: 0.202 AC: 3085 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3468

East Asian (EAS) AF: 0.00618 AC: 32 AN: 5180

South Asian (SAS) AF: 0.162 AC: 780 AN: 4816

European-Finnish (FIN) AF: 0.262 AC: 2765 AN: 10534

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19853 AN: 67954

Other (OTH) AF: 0.239 AC: 504 AN: 2110

Alfa AF: 0.273 Hom.: 10144

Bravo AF: 0.229

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.67
PhyloP100		-0.072
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: rs648576; hg19: chr1-169899427;