10-32023041-A-G

Variant names:

• chr10-32023041-A-G
• rs176924
• NM_004521.3:c.1726-5T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004521.3(KIF5B):​c.1726-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,517,138 control chromosomes in the GnomAD database, including 751,326 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (72325 hom., cov: 32)
  • Exomes 𝑓: 1.0 (679001 hom.)
• Consequence: KIF5B NM_004521.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001508
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.221
• Publications: 10 publications found

Genes affected

KIF5B (HGNC:6324): (kinesin family member 5B) Enables identical protein binding activity; microtubule binding activity; and microtubule motor activity. Involved in several processes, including lysosome localization; natural killer cell mediated cytotoxicity; and positive regulation of protein localization to plasma membrane. Located in centriolar satellite; cytosol; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-32023041-A-G is Benign according to our data. Variant chr10-32023041-A-G is described in ClinVar as Benign. ClinVar VariationId is 1302449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004521.3. 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
	KIF5B	NM_004521.3	MANE Select	c.1726-5T>C		splice_region intron	N/A	NP_004512.1	P33176

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5B	ENST00000302418.5	TSL:1 MANE Select	c.1726-5T>C		splice_region intron	N/A	ENSP00000307078.4	P33176
	KIF5B	ENST00000861449.1		c.2011-5T>C		splice_region intron	N/A	ENSP00000531508.1
	KIF5B	ENST00000861448.1		c.1726-8T>C		splice_region intron	N/A	ENSP00000531507.1

Frequencies

GnomAD3 genomes AF: 0.974 AC: 148178 AN: 152170 Hom.: 72272 Cov.: 32

Gnomad AFR AF: 0.909

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.991

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.977

GnomAD2 exomes AF: 0.993 AC: 224053 AN: 225668 AF XY: 0.995

Gnomad AFR exome AF: 0.904

Gnomad AMR exome AF: 0.995

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.997

GnomAD4 exome AF: 0.997 AC: 1361250 AN: 1364850 Hom.: 679001 Cov.: 24 AF XY: 0.998 AC XY: 672504 AN XY: 674020

African (AFR) AF: 0.904 AC: 28099 AN: 31074

American (AMR) AF: 0.995 AC: 35876 AN: 36068

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 23554 AN: 23556

East Asian (EAS) AF: 1.00 AC: 38178 AN: 38178

South Asian (SAS) AF: 1.00 AC: 67409 AN: 67416

European-Finnish (FIN) AF: 1.00 AC: 49599 AN: 49600

Middle Eastern (MID) AF: 0.999 AC: 5413 AN: 5418

European-Non Finnish (NFE) AF: 1.00 AC: 1057490 AN: 1057618

Other (OTH) AF: 0.995 AC: 55632 AN: 55922

GnomAD4 genome AF: 0.974 AC: 148290 AN: 152288 Hom.: 72325 Cov.: 32 AF XY: 0.974 AC XY: 72563 AN XY: 74462

African (AFR) AF: 0.909 AC: 37751 AN: 41544

American (AMR) AF: 0.991 AC: 15160 AN: 15302

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5188

South Asian (SAS) AF: 1.00 AC: 4826 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10602 AN: 10602

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68024 AN: 68038

Other (OTH) AF: 0.978 AC: 2061 AN: 2108

Alfa AF: 0.988 Hom.: 28192

Bravo AF: 0.970

Asia WGS AF: 0.995 AC: 3461 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.62
PhyloP100		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.030		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: rs176924; hg19: chr10-32311969;