11-62419075-A-T

Variant names:

• chr11-62419075-A-T
• rs1800593
• NM_003357.5:c.-21A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000278282.3(SCGB1A1):​c.-21A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,429,130 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SCGB1A1 ENST00000278282.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• Publications: 0 publications found

Genes affected

SCGB1A1 (HGNC:12523): (secretoglobin family 1A member 1) This gene encodes a member of the secretoglobin family of small secreted proteins. The encoded protein has been implicated in numerous functions including anti-inflammation, inhibition of phospholipase A2 and the sequestering of hydrophobic ligands. Defects in this gene are associated with a susceptibility to asthma. [provided by RefSeq, May 2010]

LOC102723765 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000278282.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCGB1A1	NM_003357.5	MANE Select	c.-21A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_003348.1
	SCGB1A1	NM_003357.5	MANE Select	c.-21A>T		5_prime_UTR	Exon 1 of 3	NP_003348.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCGB1A1	ENST00000278282.3	TSL:1 MANE Select	c.-21A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000278282.2
	SCGB1A1	ENST00000278282.3	TSL:1 MANE Select	c.-21A>T		5_prime_UTR	Exon 1 of 3	ENSP00000278282.2
	SCGB1A1	ENST00000534397.5	TSL:3	c.-51+2438A>T		intron	N/A	ENSP00000432866.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1429130 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 710276

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

African (AFR) AF: 0.00 AC: 0 AN: 32340

American (AMR) AF: 0.00 AC: 0 AN: 42078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25144

East Asian (EAS) AF: 0.00 AC: 0 AN: 38020

South Asian (SAS) AF: 0.00 AC: 0 AN: 80532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1093776

Other (OTH) AF: 0.00 AC: 0 AN: 58862

⚠️ 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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.78
PhyloP100		-0.70
PromoterAI		0.029	Neutral

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: rs1800593; hg19: chr11-62186547;