Genetic Variant ENSG00000273259:n.*711G>T (chr14-94612340-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000553947.1(ENSG00000273259):n.*711G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,210,174 control chromosomes in the GnomAD database, including 150,989 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 16535 hom., cov: 32)

Exomes 𝑓: 0.50 ( 134454 hom. )

Consequence

ENSG00000273259
ENST00000553947.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.175

Variant links:

Genes affected

ENSG00000273259 (HGNC:):

ENSG00000273259 links:

SERPINA3 (HGNC:16): (serpin family A member 3) The protein encoded by this gene is a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. This gene is one in a cluster of serpin genes located on the q arm of chromosome 14. Polymorphisms in this protein appear to be tissue specific and influence protease targeting. Variations in this protein's sequence have been implicated in Alzheimer's disease, and deficiency of this protein has been associated with liver disease. Mutations have been identified in patients with Parkinson disease and chronic obstructive pulmonary disease. [provided by RefSeq, Jun 2020]

SERPINA3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SERPINA3	NM_001085.5 link	c.-116G>T	upstream_gene_variant	ENST00000393078.5	NP_001076.2	P01011-1A0A024R6P0
SERPINA3	NM_001384672.1 link	c.-208G>T	upstream_gene_variant		NP_001371601.1
SERPINA3	NM_001384673.1 link	c.-139G>T	upstream_gene_variant		NP_001371602.1
SERPINA3	NM_001384674.1 link	c.-320G>T	upstream_gene_variant		NP_001371603.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000273259	ENST00000553947.1 link	n.*711G>T	non_coding_transcript_exon_variant	Exon 4 of 8	2		ENSP00000452367.2	G3V5I3
ENSG00000273259	ENST00000553947.1 link	n.*711G>T	3_prime_UTR_variant	Exon 4 of 8	2		ENSP00000452367.2	G3V5I3
SERPINA3	ENST00000393078.5 link	c.-116G>T	upstream_gene_variant		1	NM_001085.5	ENSP00000376793.3	P01011-1

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69145

AN:

151824

Hom.:

16526

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.456

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.463

GnomAD3 exomes

AF:

0.478

AC:

104561

AN:

218662

Hom.:

26204

AF XY:

0.487

AC XY:

57890

AN XY:

118974

show subpopulations

Gnomad AFR exome

AF:

0.339

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.648

Gnomad SAS exome

AF:

0.460

Gnomad FIN exome

AF:

0.602

Gnomad NFE exome

AF:

0.511

Gnomad OTH exome

AF:

0.487

GnomAD4 exome

AF:

0.500

AC:

528739

AN:

1058230

Hom.:

134454

Cov.:

AF XY:

0.500

AC XY:

264997

AN XY:

530010

show subpopulations

Gnomad4 AFR exome

AF:

0.327

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.561

Gnomad4 EAS exome

AF:

0.645

Gnomad4 SAS exome

AF:

0.462

Gnomad4 FIN exome

AF:

0.600

Gnomad4 NFE exome

AF:

0.511

Gnomad4 OTH exome

AF:

0.499

GnomAD4 genome

AF:

0.455

AC:

69172

AN:

151944

Hom.:

16535

Cov.:

AF XY:

0.460

AC XY:

34120

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.337

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.554

Gnomad4 EAS

AF:

0.635

Gnomad4 SAS

AF:

0.455

Gnomad4 FIN

AF:

0.602

Gnomad4 NFE

AF:

0.511

Gnomad4 OTH

AF:

0.468

Alfa

AF:

0.495

Hom.:

39756

Bravo

AF:

0.433

Asia WGS

AF:

0.510

AC:

1777

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.8

DANN

Benign

0.87

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over