chr1-10305897-T-G

Variant names:

• chr1-10305897-T-G
• rs72640311
• ENST00000377083.5:c.*1250T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000377083.5(KIF1B):​c.*1250T>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 0.015 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 ENST00000377083.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 3 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]

KIF1B Gene-Disease associations (from GenCC):

• pheochromocytoma

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease type 2A1

  Inheritance: AD Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• neuroblastoma, susceptibility to, 1

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1764 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.2115+8651T>G		intron_variant	Intron 22 of 48	ENST00000676179.1	NP_001352880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1	c.2115+8651T>G		intron_variant	Intron 22 of 48		NM_001365951.3	ENSP00000502065.1

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

African (AFR) AF: 0.00264 AC: 50 AN: 18912

American (AMR) AF: 0.00917 AC: 28 AN: 3054

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 437 AN: 9488

East Asian (EAS) AF: 0.000149 AC: 2 AN: 13384

South Asian (SAS) AF: 0.0141 AC: 240 AN: 17040

European-Finnish (FIN) AF: 0.00613 AC: 2 AN: 326

Middle Eastern (MID) AF: 0.0113 AC: 23 AN: 2044

European-Non Finnish (NFE) AF: 0.0158 AC: 12715 AN: 803676

Other (OTH) AF: 0.0158 AC: 523 AN: 33012

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

African (AFR) AF: 0.00325 AC: 135 AN: 41588

American (AMR) AF: 0.00980 AC: 150 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0124 AC: 60 AN: 4828

European-Finnish (FIN) AF: 0.00753 AC: 80 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0170 AC: 1157 AN: 68030

Other (OTH) AF: 0.0109 AC: 23 AN: 2116

Alfa AF: 0.0143 Hom.: 3

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
PhyloP100		-0.38

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: rs72640311; hg19: chr1-10365955;