14-94306167-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001756.4(SERPINA6):c.936C>T(p.Leu312=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,613,834 control chromosomes in the GnomAD database, including 54,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4230 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49860 hom.)
• Consequence: SERPINA6 NM_001756.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.163

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-94306167-G-A is Benign according to our data. Variant chr14-94306167-G-A is described in ClinVar as [Benign]. Clinvar id is 3060392.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-94306167-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.163 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA6	NM_001756.4	c.936C>T	p.Leu312=	synonymous_variant	4/5	ENST00000341584.4
SERPINA6	XM_047431827.1	c.1107C>T	p.Leu369=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA6	ENST00000341584.4	c.936C>T	p.Leu312=	synonymous_variant	4/5	1	NM_001756.4	P1
SERPINA6	ENST00000555056.1	c.*248C>T		3_prime_UTR_variant, NMD_transcript_variant	4/5	2

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34686 AN: 152022 Hom.: 4227 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.214

GnomAD3 exomes AF: 0.218 AC: 54685 AN: 251288 Hom.: 6771 AF XY: 0.218 AC XY: 29663 AN XY: 135800

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.0605

Gnomad SAS exome AF: 0.150

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.226

GnomAD4 exome AF: 0.255 AC: 373020 AN: 1461694 Hom.: 49860 Cov.: 37 AF XY: 0.252 AC XY: 183490 AN XY: 727156

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.0918

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.277

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.228 AC: 34689 AN: 152140 Hom.: 4230 Cov.: 32 AF XY: 0.222 AC XY: 16485 AN XY: 74372

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.0660

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.213

Alfa AF: 0.223 Hom.: 1542

Bravo AF: 0.220

Asia WGS AF: 0.104 AC: 363 AN: 3478

EpiCase AF: 0.269

EpiControl AF: 0.275

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SERPINA6-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.82
Dann	Benign	0.57

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: rs1042394; hg19: chr14-94772504; COSMIC: COSV58585344;