Genetic Variant NM_001195280.2:c.91-1853G>A (chr7-16530642-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001195280.2(LRRC72):c.91-1853G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,994 control chromosomes in the GnomAD database, including 16,407 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 0.46 ( 16406 hom., cov: 32)

Exomes 𝑓: 0.75 ( 1 hom. )

Consequence

LRRC72
NM_001195280.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

2 publications found

Variant links:

Genes affected

LRRC72 (HGNC:42972): (leucine rich repeat containing 72)

LRRC72 links:

SOSTDC1 (HGNC:21748): (sclerostin domain containing 1) This gene is a member of the sclerostin family and encodes an N-glycosylated, secreted protein with a C-terminal cystine knot-like domain. This protein functions as a bone morphogenetic protein (BMP) antagonist. Specifically, it directly associates with BMPs, prohibiting them from binding their receptors, thereby regulating BMP signaling during cellular proliferation, differentiation, and programmed cell death. [provided by RefSeq, Jul 2008]

SOSTDC1 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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC72	NM_001195280.2 link	c.91-1853G>A		intron_variant	Intron 1 of 8	ENST00000401542.3	NP_001182209.1	A6NJI9
LRRC72	XM_011515057.2 link	c.91-1853G>A		intron_variant	Intron 1 of 9		XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRRC72	ENST00000401542.3 link	c.91-1853G>A	intron_variant	Intron 1 of 8	5	NM_001195280.2	ENSP00000384971.2	A6NJI9
LRRC72	ENST00000382124.7 link	n.91-1853G>A	intron_variant	Intron 1 of 3	3		ENSP00000371558.3	F8VSY1
LRRC72	ENST00000482711.1 link	n.154-1853G>A	intron_variant	Intron 1 of 2	2
SOSTDC1	ENST00000396652.1 link	c.-775C>T	upstream_gene_variant		2		ENSP00000379889.1	Q6X4U4-2

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70276

AN:

151870

Hom.:

16395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.434

Gnomad AMI

AF:

0.589

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.610

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.488

Gnomad MID

AF:

0.388

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.467

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

AF XY:

0.500

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.463

AC:

70342

AN:

151990

Hom.:

16406

Cov.:

AF XY:

0.465

AC XY:

34516

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.434

AC:

17986

AN:

41456

American (AMR)

AF:

0.516

AC:

7868

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

1308

AN:

3470

East Asian (EAS)

AF:

0.610

AC:

3149

AN:

5164

South Asian (SAS)

AF:

0.394

AC:

1903

AN:

4824

European-Finnish (FIN)

AF:

0.488

AC:

5146

AN:

10542

Middle Eastern (MID)

AF:

0.401

AC:

117

AN:

292

European-Non Finnish (NFE)

AF:

0.461

AC:

31331

AN:

67956

Other (OTH)

AF:

0.472

AC:

997

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1965

3930

5896

7861

9826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.460

Hom.:

4395

Bravo

AF:

0.468

Asia WGS

AF:

0.545

AC:

1895

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.17

(source)

DANN

Benign

0.33

PhyloP100

-1.2

PromoterAI

-0.0075

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over