rs8019

Variant names:

• chr1-10306429-T-G
• rs8019
• ENST00000377083.5:c.*1782T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183416.4(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. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.39 (12023 hom., cov: 32)
  • Exomes 𝑓: 0.35 (52868 hom.)
• Consequence: KIF1B NM_183416.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183416.4. 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
	KIF1B	NM_001365951.3	MANE Select	c.2115+9183T>G		intron	N/A	NP_001352880.1	O60333-1
	KIF1B	NM_001365953.1		c.*1782T>G		3_prime_UTR	Exon 21 of 21	NP_001352882.1	O60333-3
	KIF1B	NM_183416.4		c.*1782T>G		3_prime_UTR	Exon 21 of 21	NP_904325.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1B	ENST00000377083.5	TSL:1	c.*1782T>G		3_prime_UTR	Exon 21 of 21	ENSP00000366287.1	O60333-3
	KIF1B	ENST00000377093.9	TSL:1	c.*1782T>G		3_prime_UTR	Exon 21 of 21	ENSP00000366297.4	O60333-3
	KIF1B	ENST00000676179.1	MANE Select	c.2115+9183T>G		intron	N/A	ENSP00000502065.1	O60333-1

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

African (AFR) AF: 0.463 AC: 7997 AN: 17288

American (AMR) AF: 0.368 AC: 991 AN: 2690

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 2821 AN: 8714

East Asian (EAS) AF: 0.328 AC: 4089 AN: 12452

South Asian (SAS) AF: 0.258 AC: 4171 AN: 16160

European-Finnish (FIN) AF: 0.376 AC: 115 AN: 306

Middle Eastern (MID) AF: 0.288 AC: 546 AN: 1898

European-Non Finnish (NFE) AF: 0.352 AC: 265157 AN: 753304

Other (OTH) AF: 0.361 AC: 11086 AN: 30676

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

African (AFR) AF: 0.470 AC: 19478 AN: 41426

American (AMR) AF: 0.404 AC: 6179 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1174 AN: 3464

East Asian (EAS) AF: 0.359 AC: 1858 AN: 5170

South Asian (SAS) AF: 0.280 AC: 1350 AN: 4826

European-Finnish (FIN) AF: 0.391 AC: 4118 AN: 10534

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24332 AN: 67988

Other (OTH) AF: 0.393 AC: 830 AN: 2114

Alfa AF: 0.361 Hom.: 6035

Bravo AF: 0.399

Asia WGS AF: 0.364 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.63
PhyloP100		0.55
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: rs8019; hg19: chr1-10366487;