NM_021920.4:c.*211G>C

Variant names:

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

Variant summary

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

The NM_021920.4(SCT):​c.*211G>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 594,092 control chromosomes in the GnomAD database, including 29,699 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 0.35 (10656 hom., cov: 32)
  • Exomes 𝑓: 0.28 (19043 hom.)
• 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: 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 = 0.528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021920.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCT	NM_021920.4	MANE Select	c.*211G>C		downstream_gene	N/A	NP_068739.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCT	ENST00000176195.4	TSL:1 MANE Select	c.*211G>C		downstream_gene	N/A	ENSP00000176195.3
	CDHR5	ENST00000674088.1		c.-465G>C		upstream_gene	N/A	ENSP00000501074.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53368 AN: 151982 Hom.: 10645 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.0262

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.276 AC: 122194 AN: 441992 Hom.: 19043 AF XY: 0.270 AC XY: 62563 AN XY: 231530

African (AFR) AF: 0.531 AC: 6488 AN: 12214

American (AMR) AF: 0.328 AC: 6008 AN: 18332

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 4874 AN: 13478

East Asian (EAS) AF: 0.0222 AC: 681 AN: 30720

South Asian (SAS) AF: 0.175 AC: 7532 AN: 43036

European-Finnish (FIN) AF: 0.245 AC: 8211 AN: 33546

Middle Eastern (MID) AF: 0.325 AC: 646 AN: 1990

European-Non Finnish (NFE) AF: 0.305 AC: 80133 AN: 263032

Other (OTH) AF: 0.297 AC: 7621 AN: 25644

GnomAD4 genome AF: 0.351 AC: 53404 AN: 152100 Hom.: 10656 Cov.: 32 AF XY: 0.341 AC XY: 25339 AN XY: 74358

African (AFR) AF: 0.534 AC: 22166 AN: 41480

American (AMR) AF: 0.321 AC: 4912 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1276 AN: 3468

East Asian (EAS) AF: 0.0263 AC: 136 AN: 5180

South Asian (SAS) AF: 0.159 AC: 769 AN: 4826

European-Finnish (FIN) AF: 0.226 AC: 2391 AN: 10600

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20678 AN: 67940

Other (OTH) AF: 0.346 AC: 730 AN: 2110

Alfa AF: 0.222 Hom.: 511

Bravo AF: 0.369

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.71
PhyloP100		0.65
PromoterAI		0.016	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;