14-94612340-G-T

Variant names:

• chr14-94612340-G-T
• rs1884082
• ENST00000553947.1:n.*711G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• Publications: 32 publications found

Genes affected

ENSG00000273259 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA3	NM_001085.5	c.-116G>T		upstream_gene_variant		ENST00000393078.5	NP_001076.2
SERPINA3	NM_001384672.1	c.-208G>T		upstream_gene_variant			NP_001371601.1
SERPINA3	NM_001384673.1	c.-139G>T		upstream_gene_variant			NP_001371602.1
SERPINA3	NM_001384674.1	c.-320G>T		upstream_gene_variant			NP_001371603.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69145 AN: 151824 Hom.: 16526 Cov.: 32

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

GnomAD2 exomes AF: 0.478 AC: 104561 AN: 218662 AF XY: 0.487

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 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.: 14 AF XY: 0.500 AC XY: 264997 AN XY: 530010

African (AFR) AF: 0.327 AC: 7581 AN: 23190

American (AMR) AF: 0.262 AC: 9114 AN: 34736

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 8813 AN: 15722

East Asian (EAS) AF: 0.645 AC: 10098 AN: 15660

South Asian (SAS) AF: 0.462 AC: 35681 AN: 77194

European-Finnish (FIN) AF: 0.600 AC: 18352 AN: 30590

Middle Eastern (MID) AF: 0.484 AC: 2039 AN: 4216

European-Non Finnish (NFE) AF: 0.511 AC: 417617 AN: 817958

Other (OTH) AF: 0.499 AC: 19444 AN: 38964

GnomAD4 genome AF: 0.455 AC: 69172 AN: 151944 Hom.: 16535 Cov.: 32 AF XY: 0.460 AC XY: 34120 AN XY: 74254

African (AFR) AF: 0.337 AC: 13976 AN: 41444

American (AMR) AF: 0.347 AC: 5310 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1920 AN: 3464

East Asian (EAS) AF: 0.635 AC: 3269 AN: 5146

South Asian (SAS) AF: 0.455 AC: 2189 AN: 4814

European-Finnish (FIN) AF: 0.602 AC: 6350 AN: 10544

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.511 AC: 34724 AN: 67932

Other (OTH) AF: 0.468 AC: 985 AN: 2106

Alfa AF: 0.489 Hom.: 79072

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
PhyloP100		0.17
PromoterAI		0.051	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1884082; hg19: chr14-95078677; COSMIC: COSV67585272;