chr17-18232785-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004140.4(LLGL1):​c.375C>T​(p.Pro125Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,613,954 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 28 hom., cov: 33)
Exomes 𝑓: 0.0010 ( 16 hom. )

Consequence

LLGL1
NM_004140.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.30
Variant links:
Genes affected
LLGL1 (HGNC:6628): (LLGL scribble cell polarity complex component 1) This gene encodes a protein that is similar to a tumor suppressor in Drosophila. The protein is part of a cytoskeletal network and is associated with nonmuscle myosin II heavy chain and a kinase that specifically phosphorylates this protein at serine residues. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 17-18232785-C-T is Benign according to our data. Variant chr17-18232785-C-T is described in ClinVar as [Benign]. Clinvar id is 720882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.3 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1542/152322) while in subpopulation AFR AF= 0.0346 (1440/41564). AF 95% confidence interval is 0.0332. There are 28 homozygotes in gnomad4. There are 715 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1542 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LLGL1NM_004140.4 linkc.375C>T p.Pro125Pro synonymous_variant Exon 4 of 23 ENST00000316843.9 NP_004131.4 Q15334

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LLGL1ENST00000316843.9 linkc.375C>T p.Pro125Pro synonymous_variant Exon 4 of 23 1 NM_004140.4 ENSP00000321537.4 Q15334

Frequencies

GnomAD3 genomes
AF:
0.0101
AC:
1539
AN:
152204
Hom.:
28
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0347
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00478
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00860
GnomAD3 exomes
AF:
0.00267
AC:
672
AN:
251270
Hom.:
9
AF XY:
0.00203
AC XY:
276
AN XY:
135824
show subpopulations
Gnomad AFR exome
AF:
0.0357
Gnomad AMR exome
AF:
0.00188
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000167
Gnomad OTH exome
AF:
0.000978
GnomAD4 exome
AF:
0.00101
AC:
1478
AN:
1461632
Hom.:
16
Cov.:
33
AF XY:
0.000887
AC XY:
645
AN XY:
727124
show subpopulations
Gnomad4 AFR exome
AF:
0.0336
Gnomad4 AMR exome
AF:
0.00241
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.0000564
Gnomad4 NFE exome
AF:
0.000102
Gnomad4 OTH exome
AF:
0.00200
GnomAD4 genome
AF:
0.0101
AC:
1542
AN:
152322
Hom.:
28
Cov.:
33
AF XY:
0.00960
AC XY:
715
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0346
Gnomad4 AMR
AF:
0.00477
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00851
Alfa
AF:
0.00523
Hom.:
5
Bravo
AF:
0.0119
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

May 30, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
1.6
DANN
Benign
0.47

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: rs113943896; hg19: chr17-18136099; API