Genetic Variant NM_054023.5:c.259-106C>T (chr5-147881921-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_054023.5(SCGB3A2):c.259-106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,235,692 control chromosomes in the GnomAD database, including 16,032 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3162 hom., cov: 32)

Exomes 𝑓: 0.14 ( 12870 hom. )

Consequence

SCGB3A2
NM_054023.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.866

Publications

6 publications found

Variant links:

Genes affected

SCGB3A2 (HGNC:18391): (secretoglobin family 3A member 2) The protein encoded by this gene is a secreted lung surfactant protein and a downstream target of thyroid transcription factor. A single nucleotide polymorphism in the promoter of this gene results in susceptibility to asthma.[provided by RefSeq, Mar 2010]

SCGB3A2 links:

C5orf46 (HGNC:33768): (chromosome 5 open reading frame 46) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

C5orf46 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCGB3A2	NM_054023.5 link	c.259-106C>T		intron_variant	Intron 2 of 2	ENST00000296694.5	NP_473364.1	Q96PL1Q2L6B3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCGB3A2	ENST00000296694.5 link	c.259-106C>T		intron_variant	Intron 2 of 2	1	NM_054023.5	ENSP00000296694.4		Q96PL1

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28603

AN:

151996

Hom.:

3145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.183

GnomAD4 exome

AF:

0.142

AC:

154167

AN:

1083576

Hom.:

12870

AF XY:

0.140

AC XY:

77357

AN XY:

553400

show subpopulations

African (AFR)

AF:

0.273

AC:

6930

AN:

25400

American (AMR)

AF:

0.376

AC:

15367

AN:

40906

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

2984

AN:

23302

East Asian (EAS)

AF:

0.114

AC:

4280

AN:

37468

South Asian (SAS)

AF:

0.107

AC:

8146

AN:

76264

European-Finnish (FIN)

AF:

0.151

AC:

7808

AN:

51726

Middle Eastern (MID)

AF:

0.119

AC:

515

AN:

4322

European-Non Finnish (NFE)

AF:

0.130

AC:

101108

AN:

776748

Other (OTH)

AF:

0.148

AC:

7029

AN:

47440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

6623

13246

19869

26492

33115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3212

6424

9636

12848

16060

<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:

0.188

AC:

28669

AN:

152116

Hom.:

3162

Cov.:

AF XY:

0.191

AC XY:

14215

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.273

AC:

11325

AN:

41484

American (AMR)

AF:

0.285

AC:

4359

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

461

AN:

3466

East Asian (EAS)

AF:

0.126

AC:

653

AN:

5174

South Asian (SAS)

AF:

0.113

AC:

541

AN:

4804

European-Finnish (FIN)

AF:

0.155

AC:

1644

AN:

10590

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9209

AN:

67998

Other (OTH)

AF:

0.189

AC:

398

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1169

2339

3508

4678

5847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.105

Hom.:

175

Bravo

AF:

0.202

Asia WGS

AF:

0.139

AC:

484

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.78

(source)

DANN

Benign

0.72

PhyloP100

-0.87

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over