14-94491377-G-T

Variant names:

• chr14-94491377-G-T
• rs1998207
• NM_001382267.1:c.906-1610C>A

Variant summary

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

The NM_001382267.1(SERPINA12):​c.906-1610C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,944 control chromosomes in the GnomAD database, including 9,249 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 0.34 (9249 hom., cov: 32)
• Consequence: SERPINA12 NM_001382267.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA12	NM_001382267.1	c.906-1610C>A		intron_variant	Intron 3 of 4	ENST00000677451.1	NP_001369196.1
SERPINA12	NM_001304461.2	c.906-1610C>A		intron_variant	Intron 3 of 4		NP_001291390.1
SERPINA12	NM_173850.4	c.906-1610C>A		intron_variant	Intron 4 of 5		NP_776249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA12	ENST00000677451.1	c.906-1610C>A		intron_variant	Intron 3 of 4		NM_001382267.1	ENSP00000503935.1
SERPINA12	ENST00000341228.2	c.906-1610C>A		intron_variant	Intron 4 of 5	1		ENSP00000342109.2
SERPINA12	ENST00000556881.5	c.906-1610C>A		intron_variant	Intron 3 of 4	1		ENSP00000451738.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51801 AN: 151826 Hom.: 9224 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.341 AC: 51866 AN: 151944 Hom.: 9249 Cov.: 32 AF XY: 0.343 AC XY: 25486 AN XY: 74260

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.358

Alfa AF: 0.299 Hom.: 8923

Bravo AF: 0.347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.078
DANN	Benign	0.16

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: rs1998207; hg19: chr14-94957714;