rs7951297

Variant names:

• chr11-193112-C-T
• rs7951297
• NM_145651.3:c.13C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_145651.3(SCGB1C1):​c.13C>T​(p.Arg5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (12 hom., cov: 16)
  • Exomes 𝑓: 0.026 (1667 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCGB1C1 NM_145651.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033165812).
• BP6: Variant 11-193112-C-T is Benign according to our data. Variant chr11-193112-C-T is described in ClinVar as Benign. ClinVar VariationId is 768404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.13C>T	p.Arg5Cys	missense	Exon 1 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.13C>T	p.Arg5Cys	missense	Exon 1 of 3	ENSP00000344545.2	Q8TD33
	BET1L	ENST00000410108.5	TSL:3	c.168+12499G>A		intron	N/A	ENSP00000386558.1	B8ZZS0

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 4874 AN: 89136 Hom.: 12 Cov.: 16

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0386

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.0846

Gnomad OTH AF: 0.0608

GnomAD2 exomes AF: 0.268 AC: 54057 AN: 201968 AF XY: 0.274

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.398

Gnomad EAS exome AF: 0.172

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.317

Gnomad OTH exome AF: 0.303

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0260 AC: 29572 AN: 1136558 Hom.: 1667 Cov.: 30 AF XY: 0.0280 AC XY: 15709 AN XY: 561736

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

African (AFR) AF: 0.0122 AC: 350 AN: 28642

American (AMR) AF: 0.0194 AC: 728 AN: 37498

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 1694 AN: 15316

East Asian (EAS) AF: 0.0287 AC: 860 AN: 30000

South Asian (SAS) AF: 0.0291 AC: 2019 AN: 69438

European-Finnish (FIN) AF: 0.0511 AC: 1706 AN: 33390

Middle Eastern (MID) AF: 0.0698 AC: 256 AN: 3666

European-Non Finnish (NFE) AF: 0.0232 AC: 20276 AN: 873896

Other (OTH) AF: 0.0376 AC: 1683 AN: 44712

⚠️ 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: 0.0546 AC: 4874 AN: 89240 Hom.: 12 Cov.: 16 AF XY: 0.0508 AC XY: 2198 AN XY: 43296

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

African (AFR) AF: 0.0214 AC: 626 AN: 29224

American (AMR) AF: 0.0406 AC: 366 AN: 9024

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 223 AN: 1500

East Asian (EAS) AF: 0.0379 AC: 132 AN: 3480

South Asian (SAS) AF: 0.0457 AC: 126 AN: 2760

European-Finnish (FIN) AF: 0.0374 AC: 203 AN: 5430

Middle Eastern (MID) AF: 0.167 AC: 20 AN: 120

European-Non Finnish (NFE) AF: 0.0845 AC: 3058 AN: 36176

Other (OTH) AF: 0.0609 AC: 67 AN: 1100

⚠️ 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: 0.250 Hom.: 101

ESP6500AA AF: 0.177 AC: 758

ESP6500EA AF: 0.322 AC: 2740

ExAC AF: 0.302 AC: 36557

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
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.90
DEOGEN2	Benign	0.00097	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0045	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.94	T
PhyloP100		-1.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.0030
Sift	Benign	0.15	T
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.082
MPC		0.0014
ClinPred		0.0051	T
GERP RS		-7.4
PromoterAI		-0.018	Neutral
Varity_R		0.042
gMVP		0.34
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7951297; hg19: chr11-193112; COSMIC: COSV57292562; COSMIC: COSV57292562;