rs3732341

Variant names:

• chr2-240716127-G-A
• rs3732341
• ENST00000460788.5:n.3170C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-240716127-G-A
• chr2-240716127-G-T

Variant summary

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

The ENST00000460788.5(KIF1A):​n.3170C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,770 control chromosomes in the GnomAD database, including 12,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (12148 hom., cov: 30)
  • Exomes 𝑓: 0.43 (18 hom.)
• Consequence: KIF1A ENST00000460788.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00200
• Publications: 8 publications found

Genes affected

KIF1A (HGNC:888): (kinesin family member 1A) The protein encoded by this gene is a member of the kinesin family and functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. Mutations at this locus have been associated with spastic paraplegia-30 and hereditary sensory neuropathy IIC. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]

KIF1A Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 9

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neuropathy, hereditary sensory, type 2C

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• hereditary spastic paraplegia 30

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• PEHO syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary sensory and autonomic neuropathy type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-240716127-G-A is Benign according to our data. Variant chr2-240716127-G-A is described in ClinVar as Benign. ClinVar VariationId is 335240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2	c.*1237C>T		3_prime_UTR_variant	Exon 49 of 49	ENST00000498729.9	NP_001230937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1A	ENST00000498729.9	c.*1237C>T		3_prime_UTR_variant	Exon 49 of 49	5	NM_001244008.2	ENSP00000438388.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56029 AN: 151474 Hom.: 12144 Cov.: 30

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.426 AC: 75 AN: 176 Hom.: 18 Cov.: 0 AF XY: 0.464 AC XY: 52 AN XY: 112

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.395 AC: 34 AN: 86

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.625 AC: 5 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.516 AC: 33 AN: 64

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.370 AC: 56045 AN: 151594 Hom.: 12148 Cov.: 30 AF XY: 0.368 AC XY: 27241 AN XY: 74054

African (AFR) AF: 0.160 AC: 6603 AN: 41336

American (AMR) AF: 0.406 AC: 6186 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1925 AN: 3472

East Asian (EAS) AF: 0.199 AC: 1018 AN: 5122

South Asian (SAS) AF: 0.272 AC: 1298 AN: 4776

European-Finnish (FIN) AF: 0.455 AC: 4765 AN: 10484

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32766 AN: 67838

Other (OTH) AF: 0.417 AC: 880 AN: 2110

Alfa AF: 0.439 Hom.: 14992

Bravo AF: 0.359

Asia WGS AF: 0.232 AC: 805 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary spastic paraplegia 30 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.56
PhyloP100		-0.0020
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: rs3732341; hg19: chr2-241655544;