Genetic Variant NM_021920.4:c.*211G>C (chr11-626220-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.651

Publications

17 publications found

Variant links:

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]

SCT links:

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]

CDHR5 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCT	NM_021920.4 link	c.*211G>C		downstream_gene_variant		ENST00000176195.4	NP_068739.1	P09683

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCT	ENST00000176195.4 link	c.*211G>C		downstream_gene_variant		1	NM_021920.4	ENSP00000176195.3		P09683
CDHR5	ENST00000674088.1 link	c.-465G>C		upstream_gene_variant				ENSP00000501074.1		Q9HBB8-1

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53368

AN:

151982

Hom.:

10645

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

4085

8170

12255

16340

20425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

408

816

1224

1632

2040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.351

AC:

53404

AN:

152100

Hom.:

10656

Cov.:

AF XY:

0.341

AC XY:

25339

AN XY:

74358

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1682

3364

5046

6728

8410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

494

988

1482

1976

2470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.5

(source)

DANN

Benign

0.71

PhyloP100

0.65

PromoterAI

0.016

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over