Variant 14-94377595-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000295.5(SERPINA1):c.*854T>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 0.48 in 152,084 control chromosomes in the GnomAD database, including 19,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.48 ( 19330 hom., cov: 31)

Exomes 𝑓: 0.59 ( 13 hom. )

Consequence

SERPINA1
NM_000295.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.43

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]

SERPINA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 14-94377595-A-G is Benign according to our data. Variant chr14-94377595-A-G is described in ClinVar as [Benign]. Clinvar id is 315009.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA1	NM_000295.5 linkuse as main transcript	c.*854T>C		3_prime_UTR_variant	5/5	ENST00000393087.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA1	ENST00000393087.9 linkuse as main transcript	c.*854T>C		3_prime_UTR_variant	5/5	1	NM_000295.5	P1	P01009-1

Frequencies

GnomAD3 genomes

AF:

0.480

AC:

72950

AN:

151870

Hom.:

19331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.703

Gnomad AMR

AF:

0.520

Gnomad ASJ

AF:

0.506

Gnomad EAS

AF:

0.682

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.535

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.586

Gnomad OTH

AF:

0.500

GnomAD4 exome

AF:

0.585

AC:

AN:

Hom.:

Cov.:

AF XY:

0.598

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.667

Gnomad4 NFE exome

AF:

0.595

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.480

AC:

72977

AN:

151990

Hom.:

19330

Cov.:

AF XY:

0.478

AC XY:

35538

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.520

Gnomad4 ASJ

AF:

0.506

Gnomad4 EAS

AF:

0.681

Gnomad4 SAS

AF:

0.450

Gnomad4 FIN

AF:

0.535

Gnomad4 NFE

AF:

0.586

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.518

Hom.:

4669

Bravo

AF:

0.479

Asia WGS

AF:

0.576

AC:

1999

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Alpha-1-antitrypsin deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.30

DANN

Benign

0.73

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over