rs11832

chr14-94377228-T-Cchr14-94377228-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000295.5(SERPINA1):c.*1221A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,176 control chromosomes in the GnomAD database, including 32,278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (32275 hom., cov: 33)
  • Exomes 𝑓: 0.41 (3 hom.)
• Consequence: SERPINA1 NM_000295.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 14-94377228-T-C is Benign according to our data. Variant chr14-94377228-T-C is described in ClinVar as [Benign]. Clinvar id is 315004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA1	NM_000295.5	c.*1221A>G		3_prime_UTR_variant	5/5	ENST00000393087.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA1	ENST00000393087.9	c.*1221A>G		3_prime_UTR_variant	5/5	1	NM_000295.5	P1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94899 AN: 152026 Hom.: 32210 Cov.: 33

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.626

GnomAD4 exome AF: 0.406 AC: 13 AN: 32 Hom.: 3 Cov.: 0 AF XY: 0.409 AC XY: 9 AN XY: 22

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.625 AC: 95028 AN: 152144 Hom.: 32275 Cov.: 33 AF XY: 0.624 AC XY: 46406 AN XY: 74380

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.629

Alfa AF: 0.560 Hom.: 9936

Bravo AF: 0.632

Asia WGS AF: 0.576 AC: 2005 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Alpha-1-antitrypsin deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.91
Dann	Benign	0.67

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: rs11832; hg19: chr14-94843565;