Genetic Variant NM_001005214.4:c.345G>C (chr1-165544641-G-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001005214.4(LRRC52):c.345G>C(p.Ser115Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,613,762 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0024 ( 7 hom. )

Consequence

LRRC52
NM_001005214.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0210

Publications

1 publications found

Variant links:

Genes affected

LRRC52 (HGNC:32156): (leucine rich repeat containing 52) 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]

LRRC52 links:

LRRC52-AS1 (HGNC:54044): (LRRC52 antisense RNA 1)

LRRC52-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-165544641-G-C is Benign according to our data. Variant chr1-165544641-G-C is described in ClinVar as Benign. ClinVar VariationId is 714609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.021 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005214.4. 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
	LRRC52	NM_001005214.4	MANE Select	c.345G>C	p.Ser115Ser	synonymous	Exon 1 of 2	NP_001005214.2	Q8N7C0
	LRRC52-AS1	NR_026744.2		n.960-21554C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC52	ENST00000294818.2	TSL:1 MANE Select	c.345G>C	p.Ser115Ser	synonymous	Exon 1 of 2	ENSP00000294818.2	Q8N7C0
LRRC52-AS1	ENST00000416424.5	TSL:1	n.873-21554C>G		intron	N/A
LRRC52-AS1	ENST00000438275.5	TSL:1	n.933-15759C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

236

AN:

151758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000557

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00142

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00275

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.00191

AC:

479

AN:

251432

AF XY:

0.00199

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.00368

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00243

AC:

3555

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

1736

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33480

American (AMR)

AF:

0.000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00126

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00114

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00299

AC:

3327

AN:

1112010

Other (OTH)

AF:

0.00194

AC:

117

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

231

461

692

922

1153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00155

AC:

236

AN:

151876

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.000556

AC:

AN:

41392

American (AMR)

AF:

0.0000655

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4760

European-Finnish (FIN)

AF:

0.00142

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00275

AC:

187

AN:

67956

Other (OTH)

AF:

0.000476

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00151

EpiCase

AF:

0.00245

EpiControl

AF:

0.00231

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.34

(source)

DANN

Benign

0.57

PhyloP100

-0.021

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over