Genetic Variant SERPINA6:c.614-58A>G (chr14-94310064-T-C) – 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.614-58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 1,580,424 control chromosomes in the GnomAD database, including 437,224 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 0.73 ( 40627 hom., cov: 32)

Exomes 𝑓: 0.74 ( 396597 hom. )

Consequence

SERPINA6
NM_001756.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0320

Publications

10 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: AR, AD, SD, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Orphanet

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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001756.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA6	NM_001756.4	MANE Select	c.614-58A>G		intron	N/A	NP_001747.3	P08185

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SERPINA6	ENST00000341584.4	TSL:1 MANE Select	c.614-58A>G	intron	N/A	ENSP00000342850.3	P08185
SERPINA6	ENST00000874318.1		c.763-36A>G	intron	N/A	ENSP00000544377.1
SERPINA6	ENST00000874321.1		c.614-58A>G	intron	N/A	ENSP00000544380.1

Frequencies

GnomAD3 genomes

AF:

0.726

AC:

110367

AN:

151996

Hom.:

40592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.640

Gnomad AMI

AF:

0.779

Gnomad AMR

AF:

0.794

Gnomad ASJ

AF:

0.597

Gnomad EAS

AF:

0.993

Gnomad SAS

AF:

0.785

Gnomad FIN

AF:

0.778

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.737

Gnomad OTH

AF:

0.712

GnomAD4 exome

AF:

0.743

AC:

1060902

AN:

1428308

Hom.:

396597

AF XY:

0.744

AC XY:

528752

AN XY:

710474

show subpopulations

African (AFR)

AF:

0.639

AC:

20974

AN:

32820

American (AMR)

AF:

0.847

AC:

36028

AN:

42526

Ashkenazi Jewish (ASJ)

AF:

0.596

AC:

15364

AN:

25800

East Asian (EAS)

AF:

0.996

AC:

38901

AN:

39072

South Asian (SAS)

AF:

0.777

AC:

65370

AN:

84126

European-Finnish (FIN)

AF:

0.768

AC:

39643

AN:

51602

Middle Eastern (MID)

AF:

0.690

AC:

3792

AN:

5498

European-Non Finnish (NFE)

AF:

0.733

AC:

797021

AN:

1087660

Other (OTH)

AF:

0.740

AC:

43809

AN:

59204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

14542

29084

43625

58167

72709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19620

39240

58860

78480

98100

<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:

0.726

AC:

110451

AN:

152116

Hom.:

40627

Cov.:

AF XY:

0.731

AC XY:

54383

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.640

AC:

26553

AN:

41476

American (AMR)

AF:

0.794

AC:

12149

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.597

AC:

2070

AN:

3468

East Asian (EAS)

AF:

0.993

AC:

5120

AN:

5154

South Asian (SAS)

AF:

0.785

AC:

3785

AN:

4824

European-Finnish (FIN)

AF:

0.778

AC:

8234

AN:

10590

Middle Eastern (MID)

AF:

0.677

AC:

199

AN:

294

European-Non Finnish (NFE)

AF:

0.737

AC:

50121

AN:

67990

Other (OTH)

AF:

0.714

AC:

1510

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1515

3031

4546

6062

7577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.727

Hom.:

8459

Bravo

AF:

0.724

Asia WGS

AF:

0.875

AC:

3040

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.2

(source)

DANN

Benign

0.45

PhyloP100

-0.032

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over