Genetic Variant SERPINA6:c.-20+109G>C (chr14-94323158-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001756.4(SERPINA6):c.-20+109G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,112 control chromosomes in the GnomAD database, including 22,436 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 0.54 ( 22419 hom., cov: 31)

Exomes 𝑓: 0.58 ( 17 hom. )

Consequence

SERPINA6
NM_001756.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.50

Publications

12 publications found

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 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

SERPINA6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4 link	c.-20+109G>C		intron_variant	Intron 1 of 4	ENST00000341584.4	NP_001747.3	P08185A0A2Z4LCH4
SERPINA6	XM_047431827.1 link	c.-20+109G>C		intron_variant	Intron 1 of 4		XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERPINA6	ENST00000341584.4 link	c.-20+109G>C	intron_variant	Intron 1 of 4	1	NM_001756.4	ENSP00000342850.3	P08185
SERPINA6	ENST00000557225.1 link	c.-188+109G>C	intron_variant	Intron 1 of 1	2		ENSP00000452018.1	G3V4V7
SERPINA6	ENST00000555056.1 link	n.-20+109G>C	intron_variant	Intron 1 of 4	2		ENSP00000451045.1	G3V350

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81721

AN:

151890

Hom.:

22384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.451

Gnomad AMI

AF:

0.612

Gnomad AMR

AF:

0.534

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.696

Gnomad FIN

AF:

0.560

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.578

Gnomad OTH

AF:

0.530

GnomAD4 exome

AF:

0.577

AC:

AN:

104

Hom.:

AF XY:

0.551

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.514

AC:

AN:

Other (OTH)

AF:

0.850

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.538

AC:

81802

AN:

152008

Hom.:

22419

Cov.:

AF XY:

0.539

AC XY:

40038

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.452

AC:

18715

AN:

41416

American (AMR)

AF:

0.534

AC:

8163

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

1792

AN:

3470

East Asian (EAS)

AF:

0.524

AC:

2706

AN:

5164

South Asian (SAS)

AF:

0.697

AC:

3345

AN:

4802

European-Finnish (FIN)

AF:

0.560

AC:

5926

AN:

10578

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.578

AC:

39303

AN:

67980

Other (OTH)

AF:

0.535

AC:

1129

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1917

3834

5752

7669

9586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.443

Hom.:

1307

Bravo

AF:

0.523

Asia WGS

AF:

0.618

AC:

2151

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0070

(source)

DANN

Benign

0.52

PhyloP100

-3.5

PromoterAI

-0.059

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over