rs8019

chr1-10306429-T-G

Variant summary

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

The ENST00000377083.5(KIF1B):c.*1782T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 995,492 control chromosomes in the GnomAD database, including 64,891 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 0.39 (12023 hom., cov: 32)
  • Exomes 𝑓: 0.35 (52868 hom.)
• Consequence: KIF1B ENST00000377083.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549

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]

RN7SL731P (HGNC:46747): (RNA, 7SL, cytoplasmic 731, pseudogene)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1B	NM_001365951.3	c.2115+9183T>G		intron_variant		ENST00000676179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1B	ENST00000676179.1	c.2115+9183T>G		intron_variant			NM_001365951.3	P1
RN7SL731P	ENST00000584329.2			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59716 AN: 151886 Hom.: 11978 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.388

GnomAD4 exome AF: 0.352 AC: 296973 AN: 843488 Hom.: 52868 Cov.: 14 AF XY: 0.353 AC XY: 137758 AN XY: 390646

Gnomad4 AFR exome AF: 0.463

Gnomad4 AMR exome AF: 0.368

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.328

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.361

GnomAD4 genome AF: 0.394 AC: 59820 AN: 152004 Hom.: 12023 Cov.: 32 AF XY: 0.393 AC XY: 29160 AN XY: 74282

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.393

Alfa AF: 0.360 Hom.: 5477

Bravo AF: 0.399

Asia WGS AF: 0.364 AC: 1263 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	6.6
Dann	Benign	0.63

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: rs8019; hg19: chr1-10366487;