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GeneBe

14-94314271-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001756.4(SERPINA6):c.378C>T(p.Thr126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,614,006 control chromosomes in the GnomAD database, including 33,874 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2501 hom., cov: 32)
Exomes 𝑓: 0.20 ( 31373 hom. )

Consequence

SERPINA6
NM_001756.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0110
Variant links:
Genes affected
SERPINA6 (HGNC:1540): (serpin family A member 6) This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors which may have evolved by duplication events. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-94314271-G-A is Benign according to our data. Variant chr14-94314271-G-A is described in ClinVar as [Benign]. Clinvar id is 1246534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-94314271-G-A is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.011 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SERPINA6NM_001756.4 linkuse as main transcriptc.378C>T p.Thr126= synonymous_variant 2/5 ENST00000341584.4
SERPINA6XM_047431827.1 linkuse as main transcriptc.378C>T p.Thr126= synonymous_variant 2/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SERPINA6ENST00000341584.4 linkuse as main transcriptc.378C>T p.Thr126= synonymous_variant 2/51 NM_001756.4 P1
SERPINA6ENST00000557225.1 linkuse as main transcriptc.378C>T p.Thr126= synonymous_variant 2/22
SERPINA6ENST00000555056.1 linkuse as main transcriptc.378C>T p.Thr126= synonymous_variant, NMD_transcript_variant 2/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.175
AC:
26645
AN:
152046
Hom.:
2502
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.126
Gnomad AMI
AF:
0.195
Gnomad AMR
AF:
0.140
Gnomad ASJ
AF:
0.172
Gnomad EAS
AF:
0.0930
Gnomad SAS
AF:
0.153
Gnomad FIN
AF:
0.194
Gnomad MID
AF:
0.165
Gnomad NFE
AF:
0.219
Gnomad OTH
AF:
0.158
GnomAD3 exomes
AF:
0.177
AC:
44511
AN:
251322
Hom.:
4351
AF XY:
0.179
AC XY:
24361
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.126
Gnomad AMR exome
AF:
0.113
Gnomad ASJ exome
AF:
0.164
Gnomad EAS exome
AF:
0.0861
Gnomad SAS exome
AF:
0.161
Gnomad FIN exome
AF:
0.198
Gnomad NFE exome
AF:
0.220
Gnomad OTH exome
AF:
0.180
GnomAD4 exome
AF:
0.204
AC:
297594
AN:
1461838
Hom.:
31373
Cov.:
35
AF XY:
0.203
AC XY:
147357
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.118
Gnomad4 AMR exome
AF:
0.116
Gnomad4 ASJ exome
AF:
0.165
Gnomad4 EAS exome
AF:
0.112
Gnomad4 SAS exome
AF:
0.160
Gnomad4 FIN exome
AF:
0.205
Gnomad4 NFE exome
AF:
0.218
Gnomad4 OTH exome
AF:
0.192
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.175
AC:
26646
AN:
152168
Hom.:
2501
Cov.:
32
AF XY:
0.170
AC XY:
12657
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.125
Gnomad4 AMR
AF:
0.139
Gnomad4 ASJ
AF:
0.172
Gnomad4 EAS
AF:
0.0930
Gnomad4 SAS
AF:
0.153
Gnomad4 FIN
AF:
0.194
Gnomad4 NFE
AF:
0.219
Gnomad4 OTH
AF:
0.157
Alfa
AF:
0.208
Hom.:
3866
Bravo
AF:
0.168
Asia WGS
AF:
0.140
AC:
490
AN:
3478
EpiCase
AF:
0.216
EpiControl
AF:
0.223

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJan 19, 2021- -
SERPINA6-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 23, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
6.4
Dann
Benign
0.56

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

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

Other links and lift over

dbSNP: rs3748320; hg19: chr14-94780608; COSMIC: COSV58585364; API