14-94387927-C-T

Position:

• chr14-94387927-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+633G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,972 control chromosomes in the GnomAD database, including 6,167 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 0.24 (6167 hom., cov: 31)
• Consequence: SERPINA1 ENST00000393087.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA1	NM_000295.5	c.-5+633G>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+633G>A		intron_variant		1	NM_000295.5	ENSP00000376802	P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36239 AN: 151854 Hom.: 6163 Cov.: 31

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.228

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.239 AC: 36272 AN: 151972 Hom.: 6167 Cov.: 31 AF XY: 0.234 AC XY: 17382 AN XY: 74264

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.226

Alfa AF: 0.109 Hom.: 242

Bravo AF: 0.245

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.91

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: rs3748312; hg19: chr14-94854264;