chr14-94366668-G-A

Variant names:

• chr14-94366668-G-A
• rs117457896
• ENST00000553483.4:c.31C>T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The ENST00000553483.4(SERPINA2):​c.31C>T​(p.Leu11Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 596,664 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0048 (14 hom.)
• Consequence: SERPINA2 ENST00000553483.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.343

Genes affected

SERPINA2 (HGNC:8985): (serpin family A member 2 (gene/pseudogene)) This gene encodes a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. The encoded intracellular glycoprotein is localized at the endoplasmic reticulum. This gene is a polymorphic pseudogene, with the non-functional allele being predominant in some populations. Some individuals, as represented by the reference genome allele, contain a 2kb coding region deletion and a start code mutation. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 14-94366668-G-A is Benign according to our data. Variant chr14-94366668-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644478.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.343 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA2	NR_110563.1	n.35C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA2	ENST00000553483.4	c.31C>T	p.Leu11Leu	synonymous_variant	Exon 1 of 2	5		ENSP00000486888.3

Frequencies

GnomAD3 genomes AF: 0.00407 AC: 619 AN: 152252 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00488

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.00479 AC: 2129 AN: 444294 Hom.: 14 Cov.: 0 AF XY: 0.00486 AC XY: 1168 AN XY: 240254

Gnomad4 AFR exome AF: 0.000320

Gnomad4 AMR exome AF: 0.000816

Gnomad4 ASJ exome AF: 0.000364

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00832

Gnomad4 FIN exome AF: 0.0162

Gnomad4 NFE exome AF: 0.00459

Gnomad4 OTH exome AF: 0.00423

GnomAD4 genome AF: 0.00406 AC: 619 AN: 152370 Hom.: 7 Cov.: 33 AF XY: 0.00435 AC XY: 324 AN XY: 74514

Gnomad4 AFR AF: 0.000841

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00849

Gnomad4 FIN AF: 0.0175

Gnomad4 NFE AF: 0.00488

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00434 Hom.: 0

Bravo AF: 0.00251

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SERPINA1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.79

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: rs117457896; hg19: chr14-94833005;