rs2281519

Variant names:

• chr14-94310295-G-A
• rs2281519
• NM_001756.4:c.614-289C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001756.4(SERPINA6):​c.614-289C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,128 control chromosomes in the GnomAD database, including 4,613 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 0.22 (4613 hom., cov: 32)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 6 publications found

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]

SERPINA6 Gene-Disease associations (from GenCC):

• corticosteroid-binding globulin deficiency

  Inheritance: SD, Unknown, AD, AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.614-289C>T		intron_variant	Intron 2 of 4	ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.763-267C>T		intron_variant	Intron 2 of 4		XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4	c.614-289C>T		intron_variant	Intron 2 of 4	1	NM_001756.4	ENSP00000342850.3
SERPINA6	ENST00000555056.1	n.763-289C>T		intron_variant	Intron 2 of 4	2		ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32810 AN: 152010 Hom.: 4612 Cov.: 32

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.216 AC: 32806 AN: 152128 Hom.: 4613 Cov.: 32 AF XY: 0.218 AC XY: 16201 AN XY: 74352

African (AFR) AF: 0.0551 AC: 2290 AN: 41548

American (AMR) AF: 0.310 AC: 4740 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3472

East Asian (EAS) AF: 0.482 AC: 2478 AN: 5144

South Asian (SAS) AF: 0.158 AC: 763 AN: 4820

European-Finnish (FIN) AF: 0.256 AC: 2707 AN: 10568

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18462 AN: 67984

Other (OTH) AF: 0.222 AC: 468 AN: 2112

Alfa AF: 0.257 Hom.: 10395

Bravo AF: 0.221

Asia WGS AF: 0.294 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.072
DANN	Benign	0.21
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2281519; hg19: chr14-94776632;