rs11846959

chr14-94379979-G-Achr14-94379979-G-T

Variant summary

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

The NM_000295.5(SERPINA1):c.918-368C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 142,100 control chromosomes in the GnomAD database, including 3,518 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 0.25 (3518 hom., cov: 34)
• Consequence: SERPINA1 NM_000295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA1	NM_000295.5	c.918-368C>T		intron_variant		ENST00000393087.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA1	ENST00000393087.9	c.918-368C>T		intron_variant		1	NM_000295.5	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 35153 AN: 141992 Hom.: 3505 Cov.: 34

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.248 AC: 35198 AN: 142100 Hom.: 3518 Cov.: 34 AF XY: 0.253 AC XY: 17489 AN XY: 69020

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.262

Alfa AF: 0.249 Hom.: 7705

Asia WGS AF: 0.343 AC: 1194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.5
Dann	Benign	0.44

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: rs11846959; hg19: chr14-94846316;