chr1-197084463-GTTC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_018136.5(ASPM):​c.10332-40_10332-38del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,432,470 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00054 ( 7 hom. )

Consequence

ASPM
NM_018136.5 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0310
Variant links:
Genes affected
ASPM (HGNC:19048): (assembly factor for spindle microtubules) This gene is the human ortholog of the Drosophila melanogaster 'abnormal spindle' gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts. Studies in mouse also suggest a role of this gene in mitotic spindle regulation, with a preferential role in regulating neurogenesis. Mutations in this gene are associated with microcephaly primary type 5. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 1-197084463-GTTC-G is Benign according to our data. Variant chr1-197084463-GTTC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1220309.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00521 (785/150634) while in subpopulation AFR AF= 0.0179 (737/41166). AF 95% confidence interval is 0.0168. There are 9 homozygotes in gnomad4. There are 355 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ASPMNM_018136.5 linkuse as main transcriptc.10332-40_10332-38del intron_variant ENST00000367409.9
ASPMNM_001206846.2 linkuse as main transcriptc.5577-40_5577-38del intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASPMENST00000367409.9 linkuse as main transcriptc.10332-40_10332-38del intron_variant 1 NM_018136.5 P1Q8IZT6-1

Frequencies

GnomAD3 genomes
AF:
0.00522
AC:
786
AN:
150550
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0180
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00266
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00323
Gnomad NFE
AF:
0.0000148
Gnomad OTH
AF:
0.00289
GnomAD3 exomes
AF:
0.00128
AC:
291
AN:
227884
Hom.:
3
AF XY:
0.00102
AC XY:
127
AN XY:
124398
show subpopulations
Gnomad AFR exome
AF:
0.0183
Gnomad AMR exome
AF:
0.000391
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000679
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000298
Gnomad OTH exome
AF:
0.000353
GnomAD4 exome
AF:
0.000535
AC:
686
AN:
1281836
Hom.:
7
AF XY:
0.000481
AC XY:
311
AN XY:
646094
show subpopulations
Gnomad4 AFR exome
AF:
0.0193
Gnomad4 AMR exome
AF:
0.000666
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000609
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000188
Gnomad4 OTH exome
AF:
0.00109
GnomAD4 genome
AF:
0.00521
AC:
785
AN:
150634
Hom.:
9
Cov.:
32
AF XY:
0.00484
AC XY:
355
AN XY:
73404
show subpopulations
Gnomad4 AFR
AF:
0.0179
Gnomad4 AMR
AF:
0.00265
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00287
Alfa
AF:
0.00326
Hom.:
4
Bravo
AF:
0.00640

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxMay 28, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs537718986; hg19: chr1-197053593; API