11-57181906-C-T

Variant names:

• chr11-57181906-C-T
• ENST00000652194.1:c.13C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Moderate BP6_Moderate BS2

The ENST00000652194.1(LRRC55):​c.13C>T​(p.Pro5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,446,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: LRRC55 ENST00000652194.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.977

Genes affected

LRRC55 (HGNC:32324): (leucine rich repeat containing 55) Enables potassium channel activator activity; transmembrane transporter binding activity; and voltage-gated potassium channel activity. Involved in positive regulation of voltage-gated potassium channel activity and potassium ion transmembrane transport. Part of voltage-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

LOC105369309 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098091364).
• BP6: Variant 11-57181906-C-T is Benign according to our data. Variant chr11-57181906-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2608498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC55	NM_001005210.4	c.-117C>T		upstream_gene_variant		ENST00000497933.3	NP_001005210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC55	ENST00000652194.1	c.13C>T	p.Pro5Ser	missense_variant	Exon 1 of 2			ENSP00000498533.1
LRRC55	ENST00000497933.3	c.-117C>T		upstream_gene_variant		1	NM_001005210.4	ENSP00000419542.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1446968 Hom.: 0 Cov.: 30 AF XY: 0.00000557 AC XY: 4 AN XY: 718032

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.0000353

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 29, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.96
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.91	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.068
Sift	Benign	0.23	T
Sift4G	Benign	0.96	T
Vest4		0.14
MutPred		0.23		Gain of glycosylation at P5 (P = 0.0265);
MVP		0.25
MPC		0.37
ClinPred		0.78	D
GERP RS		2.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-56949380;