rs1448746101

Variant names:

• chr2-148875592-G-C
• rs1448746101
• NM_004522.3:c.-26G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-148875592-G-C
• chr2-148875592-G-A
• chr2-148875592-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004522.3(KIF5C):​c.-26G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 0)
  • Exomes 𝑓: 0.044 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF5C NM_004522.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.17
• Publications: 1 publications found

Genes affected

KIF5C (HGNC:6325): (kinesin family member 5C) The protein encoded by this gene is a kinesin heavy chain subunit involved in the transport of cargo within the central nervous system. The encoded protein, which acts as a tetramer by associating with another heavy chain and two light chains, interacts with protein kinase CK2. Mutations in this gene have been associated with complex cortical dysplasia with other brain malformations-2. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Jul 2015]

KIF5C-AS1 (HGNC:40325): (KIF5C antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 2-148875592-G-C is Benign according to our data. Variant chr2-148875592-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 507276.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004522.3. 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
	KIF5C	NM_004522.3	MANE Select	c.-26G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	NP_004513.1	O60282-1
	KIF5C	NM_004522.3	MANE Select	c.-26G>C		5_prime_UTR	Exon 1 of 26	NP_004513.1	O60282-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5C	ENST00000435030.6	TSL:1 MANE Select	c.-26G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000435030.6	TSL:1 MANE Select	c.-26G>C		5_prime_UTR	Exon 1 of 26	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000677891.1		c.-26G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	ENSP00000503013.1	O60282-1

Frequencies

GnomAD3 genomes AF: 0.000387 AC: 20 AN: 51694 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000456

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00122

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000403

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0114 AC: 632 AN: 55206 AF XY: 0.0106

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.0511

Gnomad ASJ exome AF: 0.00566

Gnomad EAS exome AF: 0.0447

Gnomad FIN exome AF: 0.00508

Gnomad NFE exome AF: 0.00754

Gnomad OTH exome AF: 0.0205

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0440 AC: 7191 AN: 163512 Hom.: 0 Cov.: 0 AF XY: 0.0421 AC XY: 3754 AN XY: 89146

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0500 AC: 156 AN: 3118

American (AMR) AF: 0.0834 AC: 509 AN: 6100

Ashkenazi Jewish (ASJ) AF: 0.0230 AC: 141 AN: 6132

East Asian (EAS) AF: 0.0328 AC: 177 AN: 5398

South Asian (SAS) AF: 0.0618 AC: 1273 AN: 20598

European-Finnish (FIN) AF: 0.0183 AC: 281 AN: 15374

Middle Eastern (MID) AF: 0.0253 AC: 15 AN: 592

European-Non Finnish (NFE) AF: 0.0441 AC: 4360 AN: 98774

Other (OTH) AF: 0.0376 AC: 279 AN: 7426

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000387 AC: 20 AN: 51726 Hom.: 0 Cov.: 0 AF XY: 0.000434 AC XY: 11 AN XY: 25362

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000218 AC: 3 AN: 13772

American (AMR) AF: 0.000455 AC: 2 AN: 4396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1408

East Asian (EAS) AF: 0.00 AC: 0 AN: 2534

South Asian (SAS) AF: 0.00122 AC: 2 AN: 1634

European-Finnish (FIN) AF: 0.00151 AC: 3 AN: 1982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 168

European-Non Finnish (NFE) AF: 0.000403 AC: 10 AN: 24838

Other (OTH) AF: 0.00 AC: 0 AN: 670

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.87
PhyloP100		2.2
PromoterAI		0.19	Neutral
Mutation Taster		=300/0	polymorphism

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: rs1448746101; hg19: chr2-149633161;