chr14-94377481-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000295.5(SERPINA1):​c.*968T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,272 control chromosomes in the GnomAD database, including 37,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 37350 hom., cov: 32)
Exomes 𝑓: 0.64 ( 43 hom. )

Consequence

SERPINA1
NM_000295.5 3_prime_UTR

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.426
Variant links:
Genes affected
SERPINA1 (HGNC:8941): (serpin family A member 1) The protein encoded by this gene is a serine protease inhibitor belonging to the serpin superfamily whose targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, and plasminogen activator. This protein is produced in the liver, the bone marrow, by lymphocytic and monocytic cells in lymphoid tissue, and by the Paneth cells of the gut. Defects in this gene are associated with chronic obstructive pulmonary disease, emphysema, and chronic liver disease. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 14-94377481-A-G is Benign according to our data. Variant chr14-94377481-A-G is described in ClinVar as [Benign]. Clinvar id is 315008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SERPINA1NM_000295.5 linkuse as main transcriptc.*968T>C 3_prime_UTR_variant 5/5 ENST00000393087.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SERPINA1ENST00000393087.9 linkuse as main transcriptc.*968T>C 3_prime_UTR_variant 5/51 NM_000295.5 P1P01009-1

Frequencies

GnomAD3 genomes
AF:
0.698
AC:
106082
AN:
151956
Hom.:
37301
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.769
Gnomad AMI
AF:
0.702
Gnomad AMR
AF:
0.755
Gnomad ASJ
AF:
0.697
Gnomad EAS
AF:
0.650
Gnomad SAS
AF:
0.658
Gnomad FIN
AF:
0.714
Gnomad MID
AF:
0.699
Gnomad NFE
AF:
0.646
Gnomad OTH
AF:
0.712
GnomAD4 exome
AF:
0.641
AC:
127
AN:
198
Hom.:
43
Cov.:
0
AF XY:
0.639
AC XY:
92
AN XY:
144
show subpopulations
Gnomad4 AFR exome
AF:
1.00
Gnomad4 ASJ exome
AF:
1.00
Gnomad4 EAS exome
AF:
1.00
Gnomad4 FIN exome
AF:
0.714
Gnomad4 NFE exome
AF:
0.597
Gnomad4 OTH exome
AF:
0.750
GnomAD4 genome
AF:
0.698
AC:
106180
AN:
152074
Hom.:
37350
Cov.:
32
AF XY:
0.703
AC XY:
52240
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.770
Gnomad4 AMR
AF:
0.755
Gnomad4 ASJ
AF:
0.697
Gnomad4 EAS
AF:
0.650
Gnomad4 SAS
AF:
0.658
Gnomad4 FIN
AF:
0.714
Gnomad4 NFE
AF:
0.645
Gnomad4 OTH
AF:
0.704
Alfa
AF:
0.659
Hom.:
43994
Bravo
AF:
0.707
Asia WGS
AF:
0.667
AC:
2319
AN:
3478

ClinVar

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

Submissions by phenotype

Alpha-1-antitrypsin deficiency Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
2.7
DANN
Benign
0.76

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: rs1243166; hg19: chr14-94843818; API