rs74918542

Positions:

• chr6-25687818-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006998.4(SCGN):​c.528-1354T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 152,282 control chromosomes in the GnomAD database, including 2 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 0.0015 (2 hom., cov: 32)
• Consequence: SCGN NM_006998.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00153 (233/152282) while in subpopulation EAS AF= 0.0181 (94/5190). AF 95% confidence interval is 0.0152. There are 2 homozygotes in gnomad4. There are 132 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCGN	NM_006998.4	c.528-1354T>C		intron_variant		ENST00000377961.3	NP_008929.2
LOC124901284	XR_007059517.1	n.1550-5221A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCGN	ENST00000377961.3	c.528-1354T>C		intron_variant		1	NM_006998.4	ENSP00000367197.2
ENSG00000290217	ENST00000703602.1	c.528-1354T>C		intron_variant				ENSP00000515390.1
SCGN	ENST00000612225.4	n.*307-1354T>C		intron_variant		5		ENSP00000484392.1

Frequencies

GnomAD3 genomes AF: 0.00155 AC: 236 AN: 152164 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.00191

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

GnomAD4 genome AF: 0.00153 AC: 233 AN: 152282 Hom.: 2 Cov.: 32 AF XY: 0.00177 AC XY: 132 AN XY: 74468

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000937 Hom.: 0

Bravo AF: 0.00159

Asia WGS AF: 0.00492 AC: 17 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.43

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

LitVar

Other links and lift over

dbSNP: rs74918542; hg19: chr6-25688046;