Genetic Variant SCGN:c.246+15A>T (chr6-25661659-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006998.4(SCGN):c.246+15A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,544,078 control chromosomes in the GnomAD database, including 58,100 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 0.27 ( 5681 hom., cov: 32)

Exomes 𝑓: 0.27 ( 52419 hom. )

Consequence

SCGN
NM_006998.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.653

Publications

8 publications found

Variant links:

Genes affected

SCGN (HGNC:16941): (secretagogin, EF-hand calcium binding protein) The encoded protein is a secreted calcium-binding protein which is found in the cytoplasm. It is related to calbindin D-28K and calretinin. This protein is thought to be involved in KCL-stimulated calcium flux and cell proliferation. [provided by RefSeq, Jul 2008]

SCGN links:

ENSG00000290217 (HGNC:):

ENSG00000290217 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCGN	NM_006998.4 link	c.246+15A>T		intron_variant	Intron 3 of 10	ENST00000377961.3	NP_008929.2	O76038

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCGN	ENST00000377961.3 link	c.246+15A>T	intron_variant	Intron 3 of 10	1	NM_006998.4	ENSP00000367197.2	O76038
ENSG00000290217	ENST00000703602.1 link	c.246+15A>T	intron_variant	Intron 3 of 11			ENSP00000515390.1	A0A994J4C2
SCGN	ENST00000612225.4 link	n.*25+15A>T	intron_variant	Intron 2 of 9	5		ENSP00000484392.1	Q96P10

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41489

AN:

151890

Hom.:

5668

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.271

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.260

GnomAD2 exomes

AF:

0.266

AC:

66583

AN:

250030

AF XY:

0.265

show subpopulations

Gnomad AFR exome

AF:

0.304

Gnomad AMR exome

AF:

0.291

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.220

Gnomad FIN exome

AF:

0.209

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.273

AC:

379874

AN:

1392070

Hom.:

52419

Cov.:

AF XY:

0.273

AC XY:

190133

AN XY:

696542

show subpopulations

African (AFR)

AF:

0.302

AC:

9677

AN:

32062

American (AMR)

AF:

0.290

AC:

12896

AN:

44508

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

5575

AN:

25634

East Asian (EAS)

AF:

0.256

AC:

10049

AN:

39314

South Asian (SAS)

AF:

0.269

AC:

22722

AN:

84596

European-Finnish (FIN)

AF:

0.216

AC:

11524

AN:

53278

Middle Eastern (MID)

AF:

0.244

AC:

1373

AN:

5620

European-Non Finnish (NFE)

AF:

0.277

AC:

290243

AN:

1049072

Other (OTH)

AF:

0.273

AC:

15815

AN:

57986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

12812

25623

38435

51246

64058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9544

19088

28632

38176

47720

<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:

0.273

AC:

41526

AN:

152008

Hom.:

5681

Cov.:

AF XY:

0.269

AC XY:

19987

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.301

AC:

12459

AN:

41452

American (AMR)

AF:

0.271

AC:

4138

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

756

AN:

3470

East Asian (EAS)

AF:

0.245

AC:

1266

AN:

5168

South Asian (SAS)

AF:

0.273

AC:

1317

AN:

4822

European-Finnish (FIN)

AF:

0.205

AC:

2171

AN:

10584

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.275

AC:

18653

AN:

67936

Other (OTH)

AF:

0.267

AC:

565

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1560

3120

4680

6240

7800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.188

Hom.:

534

Bravo

AF:

0.280

Asia WGS

AF:

0.331

AC:

1149

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.7

(source)

DANN

Benign

0.37

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

1.0

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