Genetic Variant SERPINA6:c.-203T>C (chr14-94323450-A-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.-203T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,174 control chromosomes in the GnomAD database, including 3,617 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 0.21 ( 3616 hom., cov: 32)

Exomes 𝑓: 0.67 ( 1 hom. )

Consequence

SERPINA6
NM_001756.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.415

Publications

5 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4 link	c.-203T>C		upstream_gene_variant		ENST00000341584.4	NP_001747.3	P08185A0A2Z4LCH4
SERPINA6	XM_047431827.1 link	c.-203T>C		upstream_gene_variant			XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SERPINA6	ENST00000341584.4 link	c.-203T>C	upstream_gene_variant	1	NM_001756.4	ENSP00000342850.3	P08185
SERPINA6	ENST00000557225.1 link	c.-371T>C	upstream_gene_variant	2		ENSP00000452018.1	G3V4V7
SERPINA6	ENST00000555056.1 link	n.-203T>C	upstream_gene_variant	2		ENSP00000451045.1	G3V350

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31729

AN:

152050

Hom.:

3607

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.667

AC:

AN:

Hom.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.209

AC:

31756

AN:

152168

Hom.:

3616

Cov.:

AF XY:

0.211

AC XY:

15699

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.178

AC:

7394

AN:

41514

American (AMR)

AF:

0.151

AC:

2310

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

711

AN:

3472

East Asian (EAS)

AF:

0.388

AC:

2004

AN:

5164

South Asian (SAS)

AF:

0.362

AC:

1745

AN:

4820

European-Finnish (FIN)

AF:

0.212

AC:

2248

AN:

10588

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.214

AC:

14527

AN:

68004

Other (OTH)

AF:

0.222

AC:

468

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1310

2620

3931

5241

6551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.208

Hom.:

439

Bravo

AF:

0.197

Asia WGS

AF:

0.344

AC:

1196

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.5

(source)

DANN

Benign

0.63

PhyloP100

0.41

PromoterAI

0.10

Neutral

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over