chr14-94505905-C-A

Position:

• chr14-94505905-C-A

Variant summary

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

The NM_001382267.1(SERPINA12):​c.-34+3437G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 152,256 control chromosomes in the GnomAD database, including 609 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 0.084 (609 hom., cov: 33)
• Consequence: SERPINA12 NM_001382267.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA12	NM_001382267.1	c.-34+3437G>T		intron_variant		ENST00000677451.1	NP_001369196.1
SERPINA12	NM_173850.4	c.-17-7491G>T		intron_variant			NP_776249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA12	ENST00000677451.1	c.-34+3437G>T		intron_variant			NM_001382267.1	ENSP00000503935	P1
SERPINA12	ENST00000341228.2	c.-17-7491G>T		intron_variant		1		ENSP00000342109	P1

Frequencies

GnomAD3 genomes AF: 0.0843 AC: 12824 AN: 152138 Hom.: 610 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0799

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

GnomAD4 genome AF: 0.0843 AC: 12835 AN: 152256 Hom.: 609 Cov.: 33 AF XY: 0.0838 AC XY: 6240 AN XY: 74444

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0625

Gnomad4 ASJ AF: 0.0919

Gnomad4 EAS AF: 0.0209

Gnomad4 SAS AF: 0.0659

Gnomad4 FIN AF: 0.0792

Gnomad4 NFE AF: 0.0811

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0747 Hom.: 461

Bravo AF: 0.0829

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.048
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11627075; hg19: chr14-94972242;