11-626220-C-T

Variant names:

• chr11-626220-C-T
• rs12280580
• NM_021920.4:c.*211G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021920.4(SCT):​c.*211G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCT NM_021920.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651
• Publications: 17 publications found

Genes affected

SCT (HGNC:10607): (secretin) This gene encodes a member of the glucagon family of peptides. The encoded preproprotein is secreted by endocrine S cells in the proximal small intestinal mucosa as a prohormone, then proteolytically processed to generate the mature peptide hormone. The release of this active peptide hormone is stimulated by either fatty acids or acidic pH in the duodenum. This hormone stimulates the secretion of bile and bicarbonate in the duodenum, pancreatic and biliary ducts. [provided by RefSeq, Feb 2016]

CDHR5 (HGNC:7521): (cadherin related family member 5) This gene is a novel mucin-like gene that is a member of the cadherin superfamily. While encoding nonpolymorphic tandem repeats rich in proline, serine and threonine similar to mucin proteins, the gene also contains sequence encoding calcium-binding motifs found in all cadherins. The role of the hybrid extracellular region and the specific function of this protein have not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCT	NM_021920.4	c.*211G>A		downstream_gene_variant		ENST00000176195.4	NP_068739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCT	ENST00000176195.4	c.*211G>A		downstream_gene_variant		1	NM_021920.4	ENSP00000176195.3
CDHR5	ENST00000674088.1	c.-465G>A		upstream_gene_variant				ENSP00000501074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 442448 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 231794

African (AFR) AF: 0.00 AC: 0 AN: 12230

American (AMR) AF: 0.00 AC: 0 AN: 18352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13506

East Asian (EAS) AF: 0.00 AC: 0 AN: 30724

South Asian (SAS) AF: 0.00 AC: 0 AN: 43062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1994

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 263324

Other (OTH) AF: 0.00 AC: 0 AN: 25664

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 511

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.93
PhyloP100		0.65
PromoterAI		0.018	Neutral

Splicing

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

Other links and lift over

dbSNP: rs12280580; hg19: chr11-626220;