rs8004738

Positions:

• chr14-94390577-G-A
• chr14-94390577-G-C
• chr14-94390577-G-T

Variant summary

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

The ENST00000355814.8(SERPINA1):​c.-162C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,556 control chromosomes in the GnomAD database, including 23,234 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 0.54 (23168 hom., cov: 33)
  • Exomes 𝑓: 0.56 (66 hom.)
• Consequence: SERPINA1 ENST00000355814.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA1	NM_001002235.3	c.-125C>T		5_prime_UTR_variant	1/5		NP_001002235.1
SERPINA1	NM_001002236.3	c.-439C>T		5_prime_UTR_variant	1/7		NP_001002236.1
SERPINA1	NM_001127700.2	c.-162C>T		5_prime_UTR_variant	1/5		NP_001121172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA1	ENST00000355814.8	c.-162C>T		5_prime_UTR_variant	1/5	1		ENSP00000348068	P1
SERPINA1	ENST00000393088.8	c.-439C>T		5_prime_UTR_variant	1/7	1		ENSP00000376803	P1
SERPINA1	ENST00000404814.8	c.-226C>T		5_prime_UTR_variant	1/6	1		ENSP00000385960	P1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82488 AN: 151992 Hom.: 23132 Cov.: 33

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.531

GnomAD4 exome AF: 0.561 AC: 250 AN: 446 Hom.: 66 Cov.: 0 AF XY: 0.558 AC XY: 203 AN XY: 364

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.571

Gnomad4 SAS exome AF: 0.625

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.551

Gnomad4 OTH exome AF: 0.708

GnomAD4 genome AF: 0.543 AC: 82582 AN: 152110 Hom.: 23168 Cov.: 33 AF XY: 0.540 AC XY: 40184 AN XY: 74358

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.535

Alfa AF: 0.496 Hom.: 5975

Bravo AF: 0.533

Asia WGS AF: 0.570 AC: 1981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.6
DANN	Benign	0.86

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: rs8004738; hg19: chr14-94856914; COSMIC: COSV63345504; COSMIC: COSV63345504;