chr11-62422264-C-T

Position:

• chr11-62422264-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003357.5(SCGB1A1):​c.99C>T​(p.Thr33Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00579 in 1,613,622 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (40 hom.)
• Consequence: SCGB1A1 NM_003357.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.611

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]

ENSG00000255446 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-62422264-C-T is Benign according to our data. Variant chr11-62422264-C-T is described in ClinVar as [Benign]. Clinvar id is 791050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.611 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCGB1A1	NM_003357.5	c.99C>T	p.Thr33Thr	synonymous_variant	2/3	ENST00000278282.3	NP_003348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCGB1A1	ENST00000278282.3	c.99C>T	p.Thr33Thr	synonymous_variant	2/3	1	NM_003357.5	ENSP00000278282.2
SCGB1A1	ENST00000534397	c.-7C>T		5_prime_UTR_variant	3/4	3		ENSP00000432866.1
ENSG00000255446	ENST00000528983.1	n.91G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 697 AN: 152178 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00538

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00800

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00412 AC: 1034 AN: 251074 Hom.: 8 AF XY: 0.00416 AC XY: 564 AN XY: 135668

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000621

Gnomad FIN exome AF: 0.00707

Gnomad NFE exome AF: 0.00676

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00592 AC: 8653 AN: 1461326 Hom.: 40 Cov.: 31 AF XY: 0.00575 AC XY: 4181 AN XY: 726936

Gnomad4 AFR exome AF: 0.000926

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000754

Gnomad4 FIN exome AF: 0.00594

Gnomad4 NFE exome AF: 0.00703

Gnomad4 OTH exome AF: 0.00576

GnomAD4 genome AF: 0.00458 AC: 697 AN: 152296 Hom.: 4 Cov.: 32 AF XY: 0.00435 AC XY: 324 AN XY: 74456

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00538

Gnomad4 NFE AF: 0.00800

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00622 Hom.: 3

Bravo AF: 0.00386

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00655

EpiControl AF: 0.00593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.1
DANN	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs41465250; hg19: chr11-62189736;