rs4613

Variant names:

• chr2-240713870-A-G
• rs4613
• NM_001244008.2:c.*3494T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-240713870-A-G
• chr2-240713870-A-T

Variant summary

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

The NM_001244008.2(KIF1A):​c.*3494T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,820 control chromosomes in the GnomAD database, including 18,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (18291 hom., cov: 34)
  • Exomes 𝑓: 0.35 (36 hom.)
• Consequence: KIF1A NM_001244008.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.159
• Publications: 13 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, G2P, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

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

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

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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=-0.89).
• BP6: Variant 2-240713870-A-G is Benign according to our data. Variant chr2-240713870-A-G is described in ClinVar as Benign. ClinVar VariationId is 335210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244008.2. 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
	KIF1A	NM_001244008.2	MANE Select	c.*3494T>C		3_prime_UTR	Exon 49 of 49	NP_001230937.1	Q12756-3
	KIF1A	NM_001379631.1		c.*3494T>C		3_prime_UTR	Exon 49 of 49	NP_001366560.1
	KIF1A	NM_001379642.1		c.*3494T>C		3_prime_UTR	Exon 49 of 49	NP_001366571.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1A	ENST00000498729.9	TSL:5 MANE Select	c.*3494T>C		3_prime_UTR	Exon 49 of 49	ENSP00000438388.1	Q12756-3
	KIF1A	ENST00000460788.5	TSL:1	n.5427T>C		non_coding_transcript_exon	Exon 9 of 9
	KIF1A	ENST00000492812.6	TSL:1	n.7453T>C		non_coding_transcript_exon	Exon 16 of 16

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70787 AN: 152056 Hom.: 18248 Cov.: 34

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.466

GnomAD4 exome AF: 0.348 AC: 225 AN: 646 Hom.: 36 Cov.: 0 AF XY: 0.364 AC XY: 139 AN XY: 382

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.341 AC: 47 AN: 138

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

European-Finnish (FIN) AF: 0.337 AC: 128 AN: 380

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.365 AC: 38 AN: 104

Other (OTH) AF: 0.444 AC: 8 AN: 18

GnomAD4 genome AF: 0.466 AC: 70886 AN: 152174 Hom.: 18291 Cov.: 34 AF XY: 0.464 AC XY: 34545 AN XY: 74406

African (AFR) AF: 0.691 AC: 28660 AN: 41502

American (AMR) AF: 0.519 AC: 7935 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1810 AN: 3472

East Asian (EAS) AF: 0.267 AC: 1383 AN: 5184

South Asian (SAS) AF: 0.224 AC: 1079 AN: 4826

European-Finnish (FIN) AF: 0.399 AC: 4224 AN: 10588

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24295 AN: 67986

Other (OTH) AF: 0.465 AC: 983 AN: 2114

Alfa AF: 0.405 Hom.: 16148

Bravo AF: 0.490

Asia WGS AF: 0.290 AC: 1014 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary spastic paraplegia 30 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.41
DANN	Benign	0.35
PhyloP100		-0.16
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: rs4613; hg19: chr2-241653287; COSMIC: COSV57494241; COSMIC: COSV57494241;