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GeneBe

14-94309882-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001756.4(SERPINA6):c.738G>A(p.Ser246=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,613,854 control chromosomes in the GnomAD database, including 55,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 4666 hom., cov: 32)
Exomes 𝑓: 0.26 ( 50523 hom. )

Consequence

SERPINA6
NM_001756.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.64
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-94309882-C-T is Benign according to our data. Variant chr14-94309882-C-T is described in ClinVar as [Benign]. Clinvar id is 3060280.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-94309882-C-T 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=-5.64 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 = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SERPINA6NM_001756.4 linkuse as main transcriptc.738G>A p.Ser246= synonymous_variant 3/5 ENST00000341584.4
SERPINA6XM_047431827.1 linkuse as main transcriptc.909G>A p.Ser303= synonymous_variant 3/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SERPINA6ENST00000341584.4 linkuse as main transcriptc.738G>A p.Ser246= synonymous_variant 3/51 NM_001756.4 P1
SERPINA6ENST00000555056.1 linkuse as main transcriptc.*50G>A 3_prime_UTR_variant, NMD_transcript_variant 3/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.242
AC:
36827
AN:
151934
Hom.:
4659
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.233
Gnomad AMI
AF:
0.270
Gnomad AMR
AF:
0.187
Gnomad ASJ
AF:
0.209
Gnomad EAS
AF:
0.0661
Gnomad SAS
AF:
0.134
Gnomad FIN
AF:
0.278
Gnomad MID
AF:
0.236
Gnomad NFE
AF:
0.278
Gnomad OTH
AF:
0.225
GnomAD3 exomes
AF:
0.222
AC:
55716
AN:
251320
Hom.:
6998
AF XY:
0.221
AC XY:
30081
AN XY:
135824
show subpopulations
Gnomad AFR exome
AF:
0.235
Gnomad AMR exome
AF:
0.146
Gnomad ASJ exome
AF:
0.200
Gnomad EAS exome
AF:
0.0602
Gnomad SAS exome
AF:
0.151
Gnomad FIN exome
AF:
0.283
Gnomad NFE exome
AF:
0.278
Gnomad OTH exome
AF:
0.229
GnomAD4 exome
AF:
0.257
AC:
375968
AN:
1461802
Hom.:
50523
Cov.:
51
AF XY:
0.254
AC XY:
184825
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.236
Gnomad4 AMR exome
AF:
0.150
Gnomad4 ASJ exome
AF:
0.203
Gnomad4 EAS exome
AF:
0.0916
Gnomad4 SAS exome
AF:
0.152
Gnomad4 FIN exome
AF:
0.287
Gnomad4 NFE exome
AF:
0.277
Gnomad4 OTH exome
AF:
0.241
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.242
AC:
36843
AN:
152052
Hom.:
4666
Cov.:
32
AF XY:
0.235
AC XY:
17488
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.233
Gnomad4 AMR
AF:
0.186
Gnomad4 ASJ
AF:
0.209
Gnomad4 EAS
AF:
0.0660
Gnomad4 SAS
AF:
0.135
Gnomad4 FIN
AF:
0.278
Gnomad4 NFE
AF:
0.278
Gnomad4 OTH
AF:
0.223
Alfa
AF:
0.261
Hom.:
2752
Bravo
AF:
0.236
Asia WGS
AF:
0.109
AC:
382
AN:
3478
EpiCase
AF:
0.270
EpiControl
AF:
0.276

ClinVar

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

Submissions by phenotype

SERPINA6-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 12, 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
-0.71
Cadd
Benign
1.6
Dann
Benign
0.50
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs2228542; hg19: chr14-94776219; COSMIC: COSV58587696; COSMIC: COSV58587696; API