chr14-94322780-A-G

Variant names:

• chr14-94322780-A-G
• rs2281518
• NM_001756.4:c.-20+487T>C

Variant summary

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

The NM_001756.4(SERPINA6):​c.-20+487T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,122 control chromosomes in the GnomAD database, including 3,481 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 0.20 (3481 hom., cov: 33)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.-20+487T>C		intron_variant	Intron 1 of 4	ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.-20+487T>C		intron_variant	Intron 1 of 4		XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4	c.-20+487T>C		intron_variant	Intron 1 of 4	1	NM_001756.4	ENSP00000342850.3
SERPINA6	ENST00000557225.1	c.-188+487T>C		intron_variant	Intron 1 of 1	2		ENSP00000452018.1
SERPINA6	ENST00000555056.1	n.-20+487T>C		intron_variant	Intron 1 of 4	2		ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30707 AN: 152004 Hom.: 3472 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.202 AC: 30735 AN: 152122 Hom.: 3481 Cov.: 33 AF XY: 0.205 AC XY: 15249 AN XY: 74368

African (AFR) AF: 0.153 AC: 6343 AN: 41488

American (AMR) AF: 0.150 AC: 2289 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3470

East Asian (EAS) AF: 0.395 AC: 2043 AN: 5168

South Asian (SAS) AF: 0.368 AC: 1776 AN: 4822

European-Finnish (FIN) AF: 0.213 AC: 2254 AN: 10568

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14514 AN: 67980

Other (OTH) AF: 0.216 AC: 456 AN: 2114

Alfa AF: 0.203 Hom.: 429

Bravo AF: 0.190

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.83
PhyloP100		0.15
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: rs2281518; hg19: chr14-94789117;