rs941599

Variant names:

• chr14-94322004-C-T
• rs941599
• NM_001756.4:c.-20+1263G>A

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+1263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,146 control chromosomes in the GnomAD database, including 3,437 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 (3437 hom., cov: 33)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.-20+1263G>A		intron_variant	Intron 1 of 4	ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.-20+1263G>A		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+1263G>A		intron_variant	Intron 1 of 4	1	NM_001756.4	ENSP00000342850.3
SERPINA6	ENST00000557225.1	c.-188+1263G>A		intron_variant	Intron 1 of 1	2		ENSP00000452018.1
SERPINA6	ENST00000555056.1	n.-20+1263G>A		intron_variant	Intron 1 of 4	2		ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30461 AN: 152028 Hom.: 3428 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.200 AC: 30489 AN: 152146 Hom.: 3437 Cov.: 33 AF XY: 0.203 AC XY: 15092 AN XY: 74364

African (AFR) AF: 0.150 AC: 6217 AN: 41500

American (AMR) AF: 0.149 AC: 2281 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3464

East Asian (EAS) AF: 0.395 AC: 2042 AN: 5176

South Asian (SAS) AF: 0.357 AC: 1719 AN: 4818

European-Finnish (FIN) AF: 0.212 AC: 2247 AN: 10580

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.213 AC: 14475 AN: 68006

Other (OTH) AF: 0.215 AC: 454 AN: 2110

Alfa AF: 0.130 Hom.: 290

Bravo AF: 0.189

Asia WGS AF: 0.351 AC: 1220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.53
PhyloP100		-0.67
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: rs941599; hg19: chr14-94788341;