14-94388515-C-T

Position:

• chr14-94388515-C-T

Variant summary

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

The ENST00000393087.9(SERPINA1):​c.-5+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,912 control chromosomes in the GnomAD database, including 12,088 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 0.38 (12088 hom., cov: 31)
  • Exomes 𝑓: 0.28 (24 hom.)
  • Failed GnomAD Quality Control
• Consequence: SERPINA1 ENST00000393087.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA1	NM_000295.5	c.-5+45G>A		intron_variant		ENST00000393087.9	NP_000286.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA1	ENST00000393087.9	c.-5+45G>A		intron_variant		1	NM_000295.5	ENSP00000376802	P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58319 AN: 151794 Hom.: 12084 Cov.: 31

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.383

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.275 AC: 126 AN: 458 Hom.: 24 Cov.: 0 AF XY: 0.261 AC XY: 91 AN XY: 348

Gnomad4 AFR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.384 AC: 58357 AN: 151912 Hom.: 12088 Cov.: 31 AF XY: 0.376 AC XY: 27944 AN XY: 74248

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.388

Alfa AF: 0.337 Hom.: 11169

Bravo AF: 0.390

Asia WGS AF: 0.324 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.42

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: rs6575424; hg19: chr14-94854852;