rs3748317

Variant names:

• chr14-94387342-C-A
• rs3748317
• NM_000295.5:c.-5+1218G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-94387342-C-A
• chr14-94387342-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

SERPINA1 Gene-Disease associations (from GenCC):

• alpha 1-antitrypsin deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SERPINA1	NM_000295.5	c.-5+1218G>T		intron_variant	Intron 1 of 4	ENST00000393087.9	NP_000286.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA1	ENST00000393087.9	c.-5+1218G>T		intron_variant	Intron 1 of 4	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

African (AFR) AF: 0.158 AC: 6553 AN: 41518

American (AMR) AF: 0.130 AC: 1985 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3468

East Asian (EAS) AF: 0.273 AC: 1414 AN: 5180

South Asian (SAS) AF: 0.279 AC: 1345 AN: 4822

European-Finnish (FIN) AF: 0.103 AC: 1092 AN: 10608

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10292 AN: 67944

Other (OTH) AF: 0.170 AC: 360 AN: 2114

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
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3748317; hg19: chr14-94853679;