rs2072846

Variant names:

• chr6-25654876-T-C
• rs2072846
• NM_006998.4:c.153+1424T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006998.4(SCGN):​c.153+1424T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,048 control chromosomes in the GnomAD database, including 6,143 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 0.28 (6143 hom., cov: 32)
• Consequence: SCGN NM_006998.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 2 publications found

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]

ENSG00000290217 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCGN	NM_006998.4	c.153+1424T>C		intron_variant	Intron 2 of 10	ENST00000377961.3	NP_008929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCGN	ENST00000377961.3	c.153+1424T>C		intron_variant	Intron 2 of 10	1	NM_006998.4	ENSP00000367197.2
ENSG00000290217	ENST00000703602.1	c.153+1424T>C		intron_variant	Intron 2 of 11			ENSP00000515390.1
SCGN	ENST00000612225.4	n.82+2391T>C		intron_variant	Intron 1 of 9	5		ENSP00000484392.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42915 AN: 151930 Hom.: 6129 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.283 AC: 42957 AN: 152048 Hom.: 6143 Cov.: 32 AF XY: 0.278 AC XY: 20649 AN XY: 74320

African (AFR) AF: 0.332 AC: 13774 AN: 41454

American (AMR) AF: 0.275 AC: 4206 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3466

East Asian (EAS) AF: 0.245 AC: 1264 AN: 5158

South Asian (SAS) AF: 0.272 AC: 1314 AN: 4824

European-Finnish (FIN) AF: 0.205 AC: 2174 AN: 10596

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18690 AN: 67966

Other (OTH) AF: 0.275 AC: 579 AN: 2108

Alfa AF: 0.276 Hom.: 3064

Bravo AF: 0.291

Asia WGS AF: 0.333 AC: 1154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.24
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2072846; hg19: chr6-25655104;