Genetic Variant NM_003118.4:c.*1103C>T (chr5-151662468-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_003118.4(SPARC):c.*1103C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,454 control chromosomes in the GnomAD database, including 16,283 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 0.45 ( 16216 hom., cov: 32)

Exomes 𝑓: 0.55 ( 67 hom. )

Consequence

SPARC
NM_003118.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.80

Publications

21 publications found

Variant links:

Genes affected

SPARC (HGNC:11219): (secreted protein acidic and cysteine rich) This gene encodes a cysteine-rich acidic matrix-associated protein. The encoded protein is required for the collagen in bone to become calcified but is also involved in extracellular matrix synthesis and promotion of changes to cell shape. The gene product has been associated with tumor suppression but has also been correlated with metastasis based on changes to cell shape which can promote tumor cell invasion. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2015]

SPARC Gene-Disease associations (from GenCC):

osteogenesis imperfecta type 17
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
osteogenesis imperfecta type 4
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPARC links:

Genome browser will be placed here

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=-0.55).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SPARC	NM_003118.4 link	c.*1103C>T	3_prime_UTR_variant	Exon 10 of 10	ENST00000231061.9	NP_003109.1	P09486
SPARC	NM_001309444.2 link	c.*987C>T	3_prime_UTR_variant	Exon 10 of 10		NP_001296373.1	P09486
SPARC	NM_001309443.2 link	c.*1103C>T	3_prime_UTR_variant	Exon 10 of 10		NP_001296372.1	P09486

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARC	ENST00000231061.9 link	c.*1103C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_003118.4	ENSP00000231061.4		P09486
SPARC	ENST00000520687.1 link	n.*20C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68342

AN:

151904

Hom.:

16203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.503

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.554

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.510

Gnomad OTH

AF:

0.470

GnomAD4 exome

AF:

0.548

AC:

238

AN:

434

Hom.:

Cov.:

AF XY:

0.534

AC XY:

140

AN XY:

262

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:

0.547

AC:

233

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.450

AC:

68375

AN:

152020

Hom.:

16216

Cov.:

AF XY:

0.453

AC XY:

33630

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.290

AC:

12029

AN:

41454

American (AMR)

AF:

0.547

AC:

8364

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.503

AC:

1744

AN:

3464

East Asian (EAS)

AF:

0.431

AC:

2225

AN:

5168

South Asian (SAS)

AF:

0.372

AC:

1788

AN:

4812

European-Finnish (FIN)

AF:

0.554

AC:

5838

AN:

10544

Middle Eastern (MID)

AF:

0.517

AC:

150

AN:

290

European-Non Finnish (NFE)

AF:

0.510

AC:

34664

AN:

67982

Other (OTH)

AF:

0.474

AC:

1001

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1881

3762

5642

7523

9404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.487

Hom.:

55285

Bravo

AF:

0.443

Asia WGS

AF:

0.432

AC:

1501

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over