Genetic Variant NM_004522.3:c.-44G>A (chr2-148875574-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004522.3(KIF5C):c.-44G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 495,222 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00076 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 30 hom. )

Consequence

KIF5C
NM_004522.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.179

Publications

0 publications found

Variant links:

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 links:

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

KIF5C-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 2-148875574-G-A is Benign according to our data. Variant chr2-148875574-G-A is described in ClinVar as Benign. ClinVar VariationId is 383708.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00076 (107/140834) while in subpopulation SAS AF = 0.0252 (105/4174). AF 95% confidence interval is 0.0213. There are 2 homozygotes in GnomAd4. There are 78 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 107 AD gene.

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.-44G>A		5_prime_UTR	Exon 1 of 26	NP_004513.1	O60282-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIF5C	ENST00000435030.6	TSL:1 MANE Select	c.-44G>A	5_prime_UTR	Exon 1 of 26	ENSP00000393379.1	O60282-1
KIF5C	ENST00000677891.1		c.-44G>A	5_prime_UTR	Exon 1 of 26	ENSP00000503013.1	O60282-1
KIF5C	ENST00000677280.1		c.-44G>A	5_prime_UTR	Exon 1 of 26	ENSP00000503955.1	A0A7I2V492

Frequencies

GnomAD3 genomes

AF:

0.000760

AC:

107

AN:

140736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0252

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000512

GnomAD2 exomes

AF:

0.00343

AC:

364

AN:

106178

AF XY:

0.00443

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000353

GnomAD4 exome

AF:

0.00322

AC:

1142

AN:

354388

Hom.:

Cov.:

AF XY:

0.00459

AC XY:

894

AN XY:

194848

show subpopulations

African (AFR)

AF:

0.000112

AC:

AN:

8966

American (AMR)

AF:

0.00

AC:

AN:

20492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12384

East Asian (EAS)

AF:

0.00

AC:

AN:

16062

South Asian (SAS)

AF:

0.0226

AC:

1108

AN:

49102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30198

Middle Eastern (MID)

AF:

0.00143

AC:

AN:

1398

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

197988

Other (OTH)

AF:

0.00174

AC:

AN:

17798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000760

AC:

107

AN:

140834

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

68378

show subpopulations

African (AFR)

AF:

0.0000257

AC:

AN:

38936

American (AMR)

AF:

0.00

AC:

AN:

14310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3282

East Asian (EAS)

AF:

0.00

AC:

AN:

4334

South Asian (SAS)

AF:

0.0252

AC:

105

AN:

4174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64188

Other (OTH)

AF:

0.000507

AC:

AN:

1972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000480

Hom.:

Bravo

AF:

0.000166

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.18

PromoterAI

-0.041

Neutral

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over