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1-197084166-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_018136.5(ASPM):c.*158T>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 0.00842 in 152188 control chromosomes in the gnomAD Genomes database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting interpretations of pathogenicity (★).

Frequency

Genomes: 𝑓 0.0084 ( 14 hom., cov: 32)

Consequence

ASPM
NM_018136.5 3_prime_UTR

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -0.590

Links

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 1-197084166-A-G is Benign according to our data. Variant chr1-197084166-A-G is described in ClinVar as [Conflicting_interpretations_of_pathogenicity]. Clinvar id is 210340. Status of the report is criteria_provided_conflicting_interpretations, 1 stars. We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1, Benign=1}.
BS1
?
Variant frequency is greater than expected. gnomad allele frequency = 0.00842 (1282/152188) while in subpopulation NFE AF= 0.0133 (907/68010). AF 95% confidence interval is 0.0126. There are 14 homozygotes in gnomad. There are 588 alleles in male gnomad subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ASPMNM_018136.5 linkuse as main transcriptc.*158T>C 3_prime_UTR_variant 28/28 ENST00000367409.9
ASPMNM_001206846.2 linkuse as main transcriptc.*158T>C 3_prime_UTR_variant 27/27

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASPMENST00000367409.9 linkuse as main transcriptc.*158T>C 3_prime_UTR_variant 28/281 NM_018136.5 P1Q8IZT6-1
ASPMENST00000294732.11 linkuse as main transcriptc.*158T>C 3_prime_UTR_variant 27/271 Q8IZT6-2
ASPMENST00000367408.6 linkuse as main transcriptn.3879T>C non_coding_transcript_exon_variant 18/181
ASPMENST00000680265.1 linkuse as main transcriptc.*158T>C 3_prime_UTR_variant 29/29

Frequencies

GnomAD3 genomes
AF:
0.00842
AC:
1282
AN:
152188
Hom.:
14
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00198
Gnomad AMI
AF:
0.0230
Gnomad AMR
AF:
0.00963
Gnomad ASJ
AF:
0.0101
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00973
Gnomad FIN
AF:
0.00104
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0133
Gnomad OTH
AF:
0.0134
GnomAD4 exome
AF:
0.0113
AC:
5343
AN:
470880
Hom.:
58
AF XY:
0.0114
AC XY:
2869
AN XY:
251538
show subpopulations
Gnomad4 AFR exome
AF:
0.00179
Gnomad4 AMR exome
AF:
0.0117
Gnomad4 ASJ exome
AF:
0.0129
Gnomad4 EAS exome
AF:
0.0000321
Gnomad4 SAS exome
AF:
0.0101
Gnomad4 FIN exome
AF:
0.00168
Gnomad4 NFE exome
AF:
0.0140
Gnomad4 OTH exome
AF:
0.0125
Alfa
AF:
0.0102
Hom.:
1
Bravo
AF:
0.00897
Asia WGS
AF:
0.00290
AC:
10
AN:
3468

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2023ASPM: BS1, BS2 -
Likely benign, criteria provided, single submitterclinical testingGeneDxJul 15, 2018- -
not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoFeb 08, 2013- -
Microcephaly 5, primary, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
0.54
Dann
Benign
0.64

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: rs41265225; hg19: chr1-197053296; API