rs113943896

Variant names:

• chr17-18232785-C-T
• rs113943896
• NM_004140.4:c.375C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.30
• Publications: 0 publications found

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]

LLGL1 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004140.4. 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
	LLGL1	NM_004140.4	MANE Select	c.375C>T	p.Pro125Pro	synonymous	Exon 4 of 23	NP_004131.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LLGL1	ENST00000316843.9	TSL:1 MANE Select	c.375C>T	p.Pro125Pro	synonymous	Exon 4 of 23	ENSP00000321537.4	Q15334
	LLGL1	ENST00000855607.1		c.375C>T	p.Pro125Pro	synonymous	Exon 4 of 23	ENSP00000525666.1
	LLGL1	ENST00000855606.1		c.375C>T	p.Pro125Pro	synonymous	Exon 4 of 23	ENSP00000525665.1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1539 AN: 152204 Hom.: 28 Cov.: 33

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

GnomAD2 exomes AF: 0.00267 AC: 672 AN: 251270 AF XY: 0.00203

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 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

African (AFR) AF: 0.0336 AC: 1125 AN: 33480

American (AMR) AF: 0.00241 AC: 108 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86244

European-Finnish (FIN) AF: 0.0000564 AC: 3 AN: 53218

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.000102 AC: 113 AN: 1111976

Other (OTH) AF: 0.00200 AC: 121 AN: 60390

GnomAD4 genome AF: 0.0101 AC: 1542 AN: 152322 Hom.: 28 Cov.: 33 AF XY: 0.00960 AC XY: 715 AN XY: 74482

African (AFR) AF: 0.0346 AC: 1440 AN: 41564

American (AMR) AF: 0.00477 AC: 73 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68038

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		-3.3
Mutation Taster		=100/0	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: rs113943896; hg19: chr17-18136099;