Variant chr6-25653380-AG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_006998.4(SCGN):c.83-1delG variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.00175 in 1,595,876 control chromosomes in the GnomAD database, including 34 homozygotes. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0086 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 17 hom. )

Consequence

SCGN
NM_006998.4 splice_acceptor, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.63

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 6-25653380-AG-A is Benign according to our data. Variant chr6-25653380-AG-A is described in ClinVar as [Benign]. Clinvar id is 714310.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00861 (1312/152318) while in subpopulation AFR AF= 0.0291 (1210/41552). AF 95% confidence interval is 0.0278. There are 17 homozygotes in gnomad4. There are 582 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCGN	NM_006998.4 linkuse as main transcript	c.83-1delG		splice_acceptor_variant, intron_variant		ENST00000377961.3	NP_008929.2	O76038

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SCGN	ENST00000377961.3 linkuse as main transcript	c.83-1delG	splice_acceptor_variant, intron_variant	1	NM_006998.4	ENSP00000367197.2	O76038
ENSG00000290217	ENST00000703602.1 linkuse as main transcript	c.83-1delG	splice_acceptor_variant, intron_variant			ENSP00000515390.1	A0A994J4C2
SCGN	ENST00000612225.4 linkuse as main transcript	n.82+896delG	intron_variant	5		ENSP00000484392.1	Q96P10

Frequencies

GnomAD3 genomes

AF:

0.00862

AC:

1312

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00209

AC:

522

AN:

249946

Hom.:

AF XY:

0.00172

AC XY:

233

AN XY:

135104

show subpopulations

Gnomad AFR exome

AF:

0.0261

Gnomad AMR exome

AF:

0.00146

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000663

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00102

AC:

1479

AN:

1443558

Hom.:

Cov.:

AF XY:

0.000897

AC XY:

645

AN XY:

719292

show subpopulations

Gnomad4 AFR exome

AF:

0.0297

Gnomad4 AMR exome

AF:

0.00173

Gnomad4 ASJ exome

AF:

0.00181

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000703

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000187

Gnomad4 OTH exome

AF:

0.00253

GnomAD4 genome

AF:

0.00861

AC:

1312

AN:

152318

Hom.:

Cov.:

AF XY:

0.00781

AC XY:

582

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0291

Gnomad4 AMR

AF:

0.00385

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.000204

Hom.:

Bravo

AF:

0.00983

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

SCGN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 05, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.97

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.87

Position offset: 8

DS_AL_spliceai

0.97

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over