rs34212847

Positions:

• chr5-147882047-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The ENST00000296694.5(SCGB3A2):​c.279G>A​(p.Val93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00942 in 1,613,824 control chromosomes in the GnomAD database, including 439 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 0.018 (56 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (383 hom.)
• Consequence: SCGB3A2 ENST00000296694.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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]

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

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=-0.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCGB3A2	NM_054023.5	c.279G>A	p.Val93=	synonymous_variant	3/3	ENST00000296694.5	NP_473364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCGB3A2	ENST00000296694.5	c.279G>A	p.Val93=	synonymous_variant	3/3	1	NM_054023.5	ENSP00000296694	P1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2761 AN: 152176 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00942

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.0740

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00306

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.0151 AC: 3802 AN: 251056 Hom.: 110 AF XY: 0.0152 AC XY: 2059 AN XY: 135672

Gnomad AFR exome AF: 0.0436

Gnomad AMR exome AF: 0.00567

Gnomad ASJ exome AF: 0.00546

Gnomad EAS exome AF: 0.0769

Gnomad SAS exome AF: 0.0349

Gnomad FIN exome AF: 0.000786

Gnomad NFE exome AF: 0.00263

Gnomad OTH exome AF: 0.00767

GnomAD4 exome AF: 0.00851 AC: 12431 AN: 1461530 Hom.: 383 Cov.: 30 AF XY: 0.00907 AC XY: 6598 AN XY: 727058

Gnomad4 AFR exome AF: 0.0494

Gnomad4 AMR exome AF: 0.00588

Gnomad4 ASJ exome AF: 0.00651

Gnomad4 EAS exome AF: 0.0973

Gnomad4 SAS exome AF: 0.0357

Gnomad4 FIN exome AF: 0.000843

Gnomad4 NFE exome AF: 0.00235

Gnomad4 OTH exome AF: 0.0113

GnomAD4 genome AF: 0.0181 AC: 2764 AN: 152294 Hom.: 56 Cov.: 32 AF XY: 0.0185 AC XY: 1375 AN XY: 74474

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.00941

Gnomad4 ASJ AF: 0.00807

Gnomad4 EAS AF: 0.0743

Gnomad4 SAS AF: 0.0357

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00306

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.00802 Hom.: 10

Bravo AF: 0.0201

Asia WGS AF: 0.0640 AC: 222 AN: 3476

EpiCase AF: 0.00311

EpiControl AF: 0.00290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	2.0
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs34212847; hg19: chr5-147261610; COSMIC: COSV57023049; COSMIC: COSV57023049;