Genetic Variant SERPINA6:p.Leu312Leu (chr14-94306167-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001756.4(SERPINA6):c.936C>T(p.Leu312Leu) 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 (no stars).

Frequency

Genomes: 𝑓 0.23 ( 4230 hom., cov: 32)

Exomes 𝑓: 0.26 ( 49860 hom. )

Consequence

SERPINA6
NM_001756.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.163

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4 link	c.936C>T	p.Leu312Leu	synonymous_variant	Exon 4 of 5	ENST00000341584.4	NP_001747.3	P08185A0A2Z4LCH4
SERPINA6	XM_047431827.1 link	c.1107C>T	p.Leu369Leu	synonymous_variant	Exon 4 of 5		XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERPINA6	ENST00000341584.4 link	c.936C>T	p.Leu312Leu	synonymous_variant	Exon 4 of 5	1	NM_001756.4	ENSP00000342850.3	P08185
SERPINA6	ENST00000555056.1 link	n.*248C>T		non_coding_transcript_exon_variant	Exon 4 of 5	2		ENSP00000451045.1	G3V350
SERPINA6	ENST00000555056.1 link	n.*248C>T		3_prime_UTR_variant	Exon 4 of 5	2		ENSP00000451045.1	G3V350

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34686

AN:

152022

Hom.:

4227

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.252

AC XY:

183490

AN XY:

727156

show subpopulations

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.:

AF XY:

0.222

AC XY:

16485

AN XY:

74372

show subpopulations

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: no assertion criteria provided

LINK: link

Submissions by phenotype

SERPINA6-related disorder

Benign:1

Nov 12, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over