Genetic Variant NM_001258419.2:c.1680C>T (chr11-40114613-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001258419.2(LRRC4C):c.1680C>T(p.His560His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,614,154 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 5 hom. )

Consequence

LRRC4C
NM_001258419.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.43

Publications

3 publications found

Variant links:

Genes affected

LRRC4C (HGNC:29317): (leucine rich repeat containing 4C) NGL1 is a specific binding partner for netrin G1 (NTNG1; MIM 608818), which is a member of the netrin family of axon guidance molecules (Lin et al., 2003 [PubMed 14595443]).[supplied by OMIM, Mar 2008]

LRRC4C links:

ENSG00000306946 (HGNC:):

ENSG00000306946 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 11-40114613-G-A is Benign according to our data. Variant chr11-40114613-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2641728.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.43 with no splicing effect.

BS2

High AC in GnomAd4 at 171 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258419.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC4C	NM_001258419.2	MANE Select	c.1680C>T	p.His560His	synonymous	Exon 7 of 7	NP_001245348.1	Q9HCJ2
LRRC4C	NM_020929.3		c.1680C>T	p.His560His	synonymous	Exon 5 of 5	NP_065980.1	Q9HCJ2
LRRC4C	NR_047673.1		n.2713C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC4C	ENST00000528697.6	TSL:1 MANE Select	c.1680C>T	p.His560His	synonymous	Exon 7 of 7	ENSP00000437132.1	Q9HCJ2
LRRC4C	ENST00000278198.2	TSL:1	c.1680C>T	p.His560His	synonymous	Exon 2 of 2	ENSP00000278198.1	Q9HCJ2
LRRC4C	ENST00000527150.5	TSL:1	c.1680C>T	p.His560His	synonymous	Exon 3 of 3	ENSP00000436976.1	Q9HCJ2

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

170

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00117

AC:

293

AN:

250998

AF XY:

0.00122

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00122

AC:

1782

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

911

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39698

South Asian (SAS)

AF:

0.000800

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000711

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00141

AC:

1563

AN:

1112002

Other (OTH)

AF:

0.00126

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

124

247

371

494

618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.00112

AC:

171

AN:

152272

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000963

AC:

AN:

41550

American (AMR)

AF:

0.000262

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.00187

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000754

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00151

AC:

103

AN:

68030

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00105

Hom.:

Bravo

AF:

0.00109

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00169

EpiControl

AF:

0.00107

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.46

(source)

DANN

Benign

0.50

PhyloP100

-1.4

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

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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