Genetic Variant NM_145651.3:c.207T>C (chr11-193863-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_145651.3(SCGB1C1):c.207T>C(p.Cys69Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 9761 hom., cov: 22)

Exomes 𝑓: 0.33 ( 95531 hom. )

Failed GnomAD Quality Control

Consequence

SCGB1C1
NM_145651.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0850

Variant links:

Genes affected

SCGB1C1 (HGNC:18394): (secretoglobin family 1C member 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SCGB1C1 links:

BET1L (HGNC:19348): (Bet1 golgi vesicular membrane trafficking protein like) Enables SNAP receptor activity. Involved in regulation of retrograde vesicle-mediated transport, Golgi to ER and retrograde transport, endosome to Golgi. Located in Golgi apparatus and endosome. Implicated in uterine fibroid. Biomarker of endometrial adenocarcinoma. [provided by Alliance of Genome Resources, Apr 2022]

BET1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 11-193863-T-C is Benign according to our data. Variant chr11-193863-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 768406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.085 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCGB1C1	NM_145651.3 link	c.207T>C	p.Cys69Cys	synonymous_variant	Exon 2 of 3	ENST00000342878.3	NP_663626.2	Q8TD33
SCGB1C1	XM_005252804.4 link	c.336T>C	p.Cys112Cys	synonymous_variant	Exon 3 of 4		XP_005252861.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCGB1C1	ENST00000342878.3 link	c.207T>C	p.Cys69Cys	synonymous_variant	Exon 2 of 3	1	NM_145651.3	ENSP00000344545.2		Q8TD33
BET1L	ENST00000410108.5 link	c.168+11748A>G		intron_variant	Intron 3 of 5	3		ENSP00000386558.1		B8ZZS0

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

46365

AN:

110872

Hom.:

9737

Cov.:

FAILED QC

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.497

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.302

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.395

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.325

AC:

326273

AN:

1002696

Hom.:

95531

Cov.:

AF XY:

0.333

AC XY:

168109

AN XY:

504240

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.545

Gnomad4 ASJ exome

AF:

0.235

Gnomad4 EAS exome

AF:

0.672

Gnomad4 SAS exome

AF:

0.498

Gnomad4 FIN exome

AF:

0.415

Gnomad4 NFE exome

AF:

0.288

Gnomad4 OTH exome

AF:

0.343

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.418

AC:

46428

AN:

110986

Hom.:

9761

Cov.:

AF XY:

0.420

AC XY:

22340

AN XY:

53166

show subpopulations

Gnomad4 AFR

AF:

0.317

Gnomad4 AMR

AF:

0.498

Gnomad4 ASJ

AF:

0.295

Gnomad4 EAS

AF:

0.655

Gnomad4 SAS

AF:

0.517

Gnomad4 FIN

AF:

0.461

Gnomad4 NFE

AF:

0.442

Gnomad4 OTH

AF:

0.391

Alfa

AF:

0.506

Hom.:

3116

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.2

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over