rs45515394

Positions:

• chr14-94304833-G-T

Variant summary

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

The NM_001756.4(SERPINA6):​c.1033-230C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 152,092 control chromosomes in the GnomAD database, including 390 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 0.061 (390 hom., cov: 32)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

Genes affected

SERPINA6 (HGNC:1540): (serpin family A member 6) This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors which may have evolved by duplication events. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.1033-230C>A		intron_variant		ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.1204-230C>A		intron_variant			XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4	c.1033-230C>A		intron_variant		1	NM_001756.4	ENSP00000342850.3
SERPINA6	ENST00000555056.1	n.*345-230C>A		intron_variant		2		ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.0610 AC: 9266 AN: 151974 Hom.: 390 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.000968

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.0732

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

GnomAD4 genome AF: 0.0609 AC: 9266 AN: 152092 Hom.: 390 Cov.: 32 AF XY: 0.0594 AC XY: 4414 AN XY: 74316

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.0532

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.000970

Gnomad4 SAS AF: 0.0345

Gnomad4 FIN AF: 0.0836

Gnomad4 NFE AF: 0.0907

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0680 Hom.: 64

Bravo AF: 0.0573

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.045
DANN	Benign	0.70

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: rs45515394; hg19: chr14-94771170;