14-94387342-C-A

Position:

• chr14-94387342-C-A

Variant summary

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

The NM_000295.5(SERPINA1):​c.-5+1218G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,146 control chromosomes in the GnomAD database, including 2,047 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 0.16 (2047 hom., cov: 33)
• Consequence: SERPINA1 NM_000295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA1	NM_000295.5	c.-5+1218G>T		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+1218G>T		intron_variant		1	NM_000295.5	ENSP00000376802.4

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23664 AN: 152028 Hom.: 2039 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.156 AC: 23691 AN: 152146 Hom.: 2047 Cov.: 33 AF XY: 0.155 AC XY: 11557 AN XY: 74408

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.170

Alfa AF: 0.0607 Hom.: 75

Bravo AF: 0.155

Asia WGS AF: 0.254 AC: 885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.7
DANN	Benign	0.55

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: rs3748317; hg19: chr14-94853679;