NM_002980.3:c.624C>T

Variant names:

• chr2-119464135-G-A
• rs141567872
• NM_002980.3:c.624C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.997
• Publications: 4 publications found

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]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002980.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCTR	NM_002980.3	MANE Select	c.624C>T	p.Cys208Cys	synonymous	Exon 6 of 13	NP_002971.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCTR	ENST00000019103.8	TSL:1 MANE Select	c.624C>T	p.Cys208Cys	synonymous	Exon 6 of 13	ENSP00000019103.6
	SCTR	ENST00000903274.1		c.819C>T	p.Cys273Cys	synonymous	Exon 8 of 15	ENSP00000573333.1
	SCTR	ENST00000903275.1		c.624C>T	p.Cys208Cys	synonymous	Exon 6 of 13	ENSP00000573334.1

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 576 AN: 152208 Hom.: 4 Cov.: 32

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

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.: 31 Cov.: 32 AF XY: 0.00417 AC XY: 3031 AN XY: 727214

African (AFR) AF: 0.00105 AC: 35 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: 0 AN: 39698

South Asian (SAS) AF: 0.00337 AC: 291 AN: 86254

European-Finnish (FIN) AF: 0.000525 AC: 28 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

GnomAD4 genome AF: 0.00378 AC: 576 AN: 152326 Hom.: 4 Cov.: 32 AF XY: 0.00333 AC XY: 248 AN XY: 74486

African (AFR) AF: 0.000794 AC: 33 AN: 41570

American (AMR) AF: 0.00457 AC: 70 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4828

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00517 AC: 352 AN: 68026

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00450 Hom.: 2

Bravo AF: 0.00421

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00752

EpiControl AF: 0.00806

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.24
DANN	Benign	0.80
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs141567872; hg19: chr2-120221711; COSMIC: COSV50028080;