14-94320951-C-T

Variant names:

• chr14-94320951-C-T
• rs7161521
• NM_001756.4:c.-20+2316G>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+2316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,996 control chromosomes in the GnomAD database, including 3,450 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 (3450 hom., cov: 31)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 10 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=-0.89).
• 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+2316G>A		intron_variant	Intron 1 of 4	ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.-20+2316G>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+2316G>A		intron_variant	Intron 1 of 4	1	NM_001756.4	ENSP00000342850.3
SERPINA6	ENST00000557225.1	c.-188+2316G>A		intron_variant	Intron 1 of 1	2		ENSP00000452018.1
SERPINA6	ENST00000555056.1	n.-20+2316G>A		intron_variant	Intron 1 of 4	2		ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30481 AN: 151878 Hom.: 3441 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.214

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: 0.201 AC: 30508 AN: 151996 Hom.: 3450 Cov.: 31 AF XY: 0.203 AC XY: 15115 AN XY: 74286

African (AFR) AF: 0.149 AC: 6197 AN: 41466

American (AMR) AF: 0.149 AC: 2281 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3468

East Asian (EAS) AF: 0.394 AC: 2025 AN: 5136

South Asian (SAS) AF: 0.363 AC: 1746 AN: 4812

European-Finnish (FIN) AF: 0.214 AC: 2257 AN: 10566

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

European-Non Finnish (NFE) AF: 0.213 AC: 14492 AN: 67956

Other (OTH) AF: 0.214 AC: 453 AN: 2112

Alfa AF: 0.203 Hom.: 4081

Bravo AF: 0.189

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.96
PhyloP100		0.18
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: rs7161521; hg19: chr14-94787288;