Genetic Variant SCTR:p.Cys208Cys (chr2-119464135-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002980.3(SCTR):c.624C>T(p.Cys208Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,614,134 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 31 hom. )

Consequence

SCTR
NM_002980.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.997

Publications

4 publications found

Variant links:

Genes affected

SCTR (HGNC:10608): (secretin receptor) The protein encoded by this gene is a G protein-coupled receptor and belongs to the glucagon-VIP-secretin receptor family. It binds secretin which is the most potent regulator of pancreatic bicarbonate, electrolyte and volume secretion. Secretin and its receptor are suggested to be involved in pancreatic cancer and autism. [provided by RefSeq, Jul 2008]

SCTR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-119464135-G-A is Benign according to our data. Variant chr2-119464135-G-A is described in ClinVar as Benign. ClinVar VariationId is 710545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.997 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00411 (6014/1461808) while in subpopulation MID AF = 0.0265 (153/5766). AF 95% confidence interval is 0.0231. There are 31 homozygotes in GnomAdExome4. There are 3031 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCTR	NM_002980.3 link	c.624C>T	p.Cys208Cys	synonymous_variant	Exon 6 of 13	ENST00000019103.8	NP_002971.2	P47872Q8IV17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCTR	ENST00000019103.8 link	c.624C>T	p.Cys208Cys	synonymous_variant	Exon 6 of 13	1	NM_002980.3	ENSP00000019103.6	P47872
SCTR	ENST00000627145.1 link	c.699C>T	p.Cys233Cys	synonymous_variant	Exon 7 of 8	5		ENSP00000486987.1	A0A0D9SFY2
SCTR	ENST00000630739.2 link	c.420C>T	p.Cys140Cys	synonymous_variant	Exon 7 of 8	5		ENSP00000486930.1	A0A0D9SFV7
SCTR	ENST00000485440.1 link	n.1304C>T		non_coding_transcript_exon_variant	Exon 3 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

576

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00517

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00382

AC:

961

AN:

251380

AF XY:

0.00400

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000556

Gnomad NFE exome

AF:

0.00549

Gnomad OTH exome

AF:

0.00652

GnomAD4 exome

AF:

0.00411

AC:

6014

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

3031

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00105

AC:

AN:

33480

American (AMR)

AF:

0.00335

AC:

150

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00727

AC:

190

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00337

AC:

291

AN:

86254

European-Finnish (FIN)

AF:

0.000525

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.0265

AC:

153

AN:

5766

European-Non Finnish (NFE)

AF:

0.00438

AC:

4873

AN:

1111986

Other (OTH)

AF:

0.00487

AC:

294

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

296

592

888

1184

1480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<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:

0.00378

AC:

576

AN:

152326

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

248

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41570

American (AMR)

AF:

0.00457

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00290

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00517

AC:

352

AN:

68026

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00450

Hom.:

Bravo

AF:

0.00421

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00752

EpiControl

AF:

0.00806

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 25, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.24

(source)

DANN

Benign

0.80

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over