rs2236242

Positions:

• chr14-94493715-T-A

Variant summary

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

The NM_001382267.1(SERPINA12):​c.905+2658A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,150 control chromosomes in the GnomAD database, including 8,601 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 0.31 (8601 hom., cov: 33)
• Consequence: SERPINA12 NM_001382267.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181

Genes affected

SERPINA12 (HGNC:18359): (serpin family A member 12) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to act upstream of or within negative regulation of gluconeogenesis; positive regulation of signal transduction; and regulation of lipid metabolic process. Predicted to be located in plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA12	NM_001382267.1	c.905+2658A>T		intron_variant		ENST00000677451.1
SERPINA12	NM_001304461.2	c.905+2658A>T		intron_variant
SERPINA12	NM_173850.4	c.905+2658A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA12	ENST00000677451.1	c.905+2658A>T		intron_variant			NM_001382267.1	P1
SERPINA12	ENST00000341228.2	c.905+2658A>T		intron_variant		1		P1
SERPINA12	ENST00000556881.5	c.905+2658A>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47100 AN: 152032 Hom.: 8597 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.310 AC: 47113 AN: 152150 Hom.: 8601 Cov.: 33 AF XY: 0.311 AC XY: 23162 AN XY: 74374

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.321

Alfa AF: 0.350 Hom.: 1345

Bravo AF: 0.296

Asia WGS AF: 0.305 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.63

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: rs2236242; hg19: chr14-94960052;