chr11-62422407-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_003357.5(SCGB1A1):ā€‹c.242T>Cā€‹(p.Met81Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,610,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000040 ( 0 hom., cov: 32)
Exomes š‘“: 0.000020 ( 0 hom. )

Consequence

SCGB1A1
NM_003357.5 missense, splice_region

Scores

18
Splicing: ADA: 0.00001204
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.76
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.026704878).
BP6
Variant 11-62422407-T-C is Benign according to our data. Variant chr11-62422407-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3158399.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCGB1A1NM_003357.5 linkuse as main transcriptc.242T>C p.Met81Thr missense_variant, splice_region_variant 2/3 ENST00000278282.3
LOC102723765XR_007062699.1 linkuse as main transcriptn.237+4280A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCGB1A1ENST00000278282.3 linkuse as main transcriptc.242T>C p.Met81Thr missense_variant, splice_region_variant 2/31 NM_003357.5 P1
ENST00000528983.1 linkuse as main transcriptn.39-91A>G intron_variant, non_coding_transcript_variant 3
SCGB1A1ENST00000534397.5 linkuse as main transcriptc.137T>C p.Met46Thr missense_variant, splice_region_variant 3/43

Frequencies

GnomAD3 genomes
AF:
0.0000398
AC:
6
AN:
150840
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00116
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000681
AC:
17
AN:
249620
Hom.:
0
AF XY:
0.0000667
AC XY:
9
AN XY:
134940
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000292
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000816
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000199
AC:
29
AN:
1459456
Hom.:
0
Cov.:
31
AF XY:
0.0000248
AC XY:
18
AN XY:
725852
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000706
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000398
AC:
6
AN:
150840
Hom.:
0
Cov.:
32
AF XY:
0.0000271
AC XY:
2
AN XY:
73692
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000491
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJan 03, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.69
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.0090
DANN
Benign
0.45
DEOGEN2
Benign
0.0059
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0029
N
LIST_S2
Benign
0.28
T;T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.027
T;T
MetaSVM
Benign
-0.93
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
1.2
N;N
REVEL
Benign
0.041
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0010
.;B
Vest4
0.18
MutPred
0.59
.;Gain of ubiquitination at K83 (P = 0.0624);
MVP
0.055
MPC
0.14
ClinPred
0.031
T
GERP RS
-4.0
Varity_R
0.031
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000012
dbscSNV1_RF
Benign
0.0
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs760802019; hg19: chr11-62189879; API