rs72640311

Positions:

• chr1-10305897-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001365951.3(KIF1B):​c.2115+8651T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,053,294 control chromosomes in the GnomAD database, including 134 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 0.012 (10 hom., cov: 32)
  • Exomes 𝑓: 0.016 (124 hom.)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

Genes affected

KIF1B (HGNC:16636): (kinesin family member 1B) Predicted to enable microtubule binding activity and plus-end-directed microtubule motor activity. Predicted to be involved in chemical synaptic transmission; dense core granule cytoskeletal transport; and vesicle-mediated transport. Predicted to act upstream of or within mitochondrion transport along microtubule. Predicted to be located in cytoplasmic vesicle membrane and neuron projection. Predicted to be part of kinesin complex. Predicted to be active in several cellular components, including axon; dendrite; and microtubule. Implicated in Charcot-Marie-Tooth disease type 2A1; carcinoma (multiple); multiple sclerosis; neuroblastoma; and pheochromocytoma. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0116 (1764/152358) while in subpopulation NFE AF= 0.017 (1157/68030). AF 95% confidence interval is 0.0162. There are 10 homozygotes in gnomad4. There are 820 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1764 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.2115+8651T>G		intron_variant		ENST00000676179.1	NP_001352880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1	c.2115+8651T>G		intron_variant			NM_001365951.3	ENSP00000502065	P1

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1765 AN: 152238 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00753

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.0156 AC: 14020 AN: 900936 Hom.: 124 Cov.: 32 AF XY: 0.0154 AC XY: 6421 AN XY: 416004

Gnomad4 AFR exome AF: 0.00264

Gnomad4 AMR exome AF: 0.00917

Gnomad4 ASJ exome AF: 0.0461

Gnomad4 EAS exome AF: 0.000149

Gnomad4 SAS exome AF: 0.0141

Gnomad4 FIN exome AF: 0.00613

Gnomad4 NFE exome AF: 0.0158

Gnomad4 OTH exome AF: 0.0158

GnomAD4 genome AF: 0.0116 AC: 1764 AN: 152358 Hom.: 10 Cov.: 32 AF XY: 0.0110 AC XY: 820 AN XY: 74500

Gnomad4 AFR AF: 0.00325

Gnomad4 AMR AF: 0.00980

Gnomad4 ASJ AF: 0.0438

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.00753

Gnomad4 NFE AF: 0.0170

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0127 Hom.: 0

Bravo AF: 0.0112

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.4
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs72640311; hg19: chr1-10365955;