Genetic Variant NM_001195545.2:c.-175+1724A>C (chr17-39929538-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001195545.2(LRRC3C):c.-175+1724A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,090 control chromosomes in the GnomAD database, including 43,691 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.76 ( 43683 hom., cov: 32)

Exomes 𝑓: 0.94 ( 8 hom. )

Consequence

LRRC3C
NM_001195545.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0950

Publications

14 publications found

Variant links:

Genes affected

LRRC3C (HGNC:40034): (leucine rich repeat containing 3C) Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LRRC3C links:

ENSG00000264968 (HGNC:):

ENSG00000264968 links:

ORMDL3 (HGNC:16038): (ORMDL sphingolipid biosynthesis regulator 3) Involved in ceramide metabolic process. Acts upstream of or within several processes, including negative regulation of B cell apoptotic process; negative regulation of ceramide biosynthetic process; and positive regulation of protein localization to nucleus. Located in endoplasmic reticulum. Part of SPOTS complex. [provided by Alliance of Genome Resources, Apr 2022]

ORMDL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195545.2. 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
	LRRC3C	NM_001195545.2	MANE Select	c.-175+1724A>C		intron	N/A	NP_001182474.1	A6NJW4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LRRC3C	ENST00000377924.6	TSL:3 MANE Select	c.-175+1724A>C	intron	N/A	ENSP00000367157.4	A6NJW4
ENSG00000264968	ENST00000582263.1	TSL:5	n.161+305A>C	intron	N/A
ENSG00000264968	ENST00000790964.1		n.22+1637A>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.757

AC:

114993

AN:

151954

Hom.:

43673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.703

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.724

Gnomad ASJ

AF:

0.767

Gnomad EAS

AF:

0.736

Gnomad SAS

AF:

0.774

Gnomad FIN

AF:

0.758

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.797

Gnomad OTH

AF:

0.763

GnomAD4 exome

AF:

0.944

AC:

AN:

Hom.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.900

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.756

AC:

115042

AN:

152072

Hom.:

43683

Cov.:

AF XY:

0.752

AC XY:

55907

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.702

AC:

29094

AN:

41438

American (AMR)

AF:

0.723

AC:

11053

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.767

AC:

2660

AN:

3466

East Asian (EAS)

AF:

0.736

AC:

3820

AN:

5190

South Asian (SAS)

AF:

0.774

AC:

3733

AN:

4824

European-Finnish (FIN)

AF:

0.758

AC:

7998

AN:

10556

Middle Eastern (MID)

AF:

0.816

AC:

240

AN:

294

European-Non Finnish (NFE)

AF:

0.797

AC:

54223

AN:

67998

Other (OTH)

AF:

0.762

AC:

1610

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1456

2911

4367

5822

7278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<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:

0.773

Hom.:

10989

Bravo

AF:

0.754

Asia WGS

AF:

0.721

AC:

2510

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.87

(source)

DANN

Benign

0.58

PhyloP100

-0.095

Splicing

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