rs17751769

Positions:

• chr14-94390320-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000355814.8(SERPINA1):​c.-5+100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,834 control chromosomes in the GnomAD database, including 15,998 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 0.45 (15998 hom., cov: 33)
  • Exomes 𝑓: 0.39 (20 hom.)
  • Failed GnomAD Quality Control
• Consequence: SERPINA1 ENST00000355814.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA1	NM_001002235.3	c.-5+137C>T		intron_variant
SERPINA1	NM_001002236.3	c.-319+137C>T		intron_variant
SERPINA1	NM_001127700.2	c.-5+100C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA1	ENST00000355814.8	c.-5+100C>T		intron_variant		1		P1
SERPINA1	ENST00000393088.8	c.-319+137C>T		intron_variant		1		P1
SERPINA1	ENST00000404814.8	c.-106+137C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68531 AN: 151716 Hom.: 15990 Cov.: 33

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.441

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.390 AC: 114 AN: 292 Hom.: 20 AF XY: 0.402 AC XY: 86 AN XY: 214

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.833

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 0.545

GnomAD4 genome AF: 0.452 AC: 68580 AN: 151834 Hom.: 15998 Cov.: 33 AF XY: 0.450 AC XY: 33362 AN XY: 74192

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.444

Alfa AF: 0.419 Hom.: 16615

Bravo AF: 0.446

Asia WGS AF: 0.489 AC: 1701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs17751769; hg19: chr14-94856657;