chr11-193722-A-G

Variant names:

• chr11-193722-A-G
• rs2294082
• NM_145651.3:c.66A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_145651.3(SCGB1C1):​c.66A>G​(p.Thr22Thr) 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (1 hom., cov: 29)
  • Exomes 𝑓: 0.0029 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCGB1C1 NM_145651.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.04
• Publications: 8 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 11-193722-A-G is Benign according to our data. Variant chr11-193722-A-G is described in ClinVar as Benign. ClinVar VariationId is 768405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.04 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145651.3. 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
	SCGB1C1	NM_145651.3	MANE Select	c.66A>G	p.Thr22Thr	synonymous	Exon 2 of 3	NP_663626.2	Q8TD33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCGB1C1	ENST00000342878.3	TSL:1 MANE Select	c.66A>G	p.Thr22Thr	synonymous	Exon 2 of 3	ENSP00000344545.2	Q8TD33
	BET1L	ENST00000410108.5	TSL:3	c.168+11889T>C		intron	N/A	ENSP00000386558.1	B8ZZS0

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 3220 AN: 120966 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0343

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0111

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.0780

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.193 AC: 43760 AN: 227120 AF XY: 0.191

Gnomad AFR exome AF: 0.187

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.405

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.177

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00289 AC: 4044 AN: 1398092 Hom.: 1 Cov.: 34 AF XY: 0.00294 AC XY: 2036 AN XY: 693086

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00302 AC: 96 AN: 31794

American (AMR) AF: 0.00548 AC: 225 AN: 41094

Ashkenazi Jewish (ASJ) AF: 0.00214 AC: 53 AN: 24724

East Asian (EAS) AF: 0.0683 AC: 1906 AN: 27924

South Asian (SAS) AF: 0.00198 AC: 154 AN: 77894

European-Finnish (FIN) AF: 0.00298 AC: 148 AN: 49734

Middle Eastern (MID) AF: 0.00568 AC: 29 AN: 5110

European-Non Finnish (NFE) AF: 0.00112 AC: 1217 AN: 1082998

Other (OTH) AF: 0.00380 AC: 216 AN: 56820

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0266 AC: 3224 AN: 121066 Hom.: 1 Cov.: 29 AF XY: 0.0290 AC XY: 1712 AN XY: 58936

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0274 AC: 895 AN: 32654

American (AMR) AF: 0.0520 AC: 586 AN: 11274

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 32 AN: 2886

East Asian (EAS) AF: 0.150 AC: 491 AN: 3270

South Asian (SAS) AF: 0.0781 AC: 251 AN: 3214

European-Finnish (FIN) AF: 0.0117 AC: 107 AN: 9178

Middle Eastern (MID) AF: 0.00410 AC: 1 AN: 244

European-Non Finnish (NFE) AF: 0.0142 AC: 796 AN: 55944

Other (OTH) AF: 0.0241 AC: 41 AN: 1702

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.104 Hom.: 0

ClinVar

ClinVar submissions

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	-0.95
CADD	Benign	2.2
DANN	Benign	0.46
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2294082; hg19: chr11-193722; COSMIC: COSV57292361; COSMIC: COSV57292361;