dbSNP rs11160169: SERPINA6:c.614-98G>T (chr14-94310104-C-A) – 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.614-98G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,242,462 control chromosomes in the GnomAD database, including 154,171 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 0.47 ( 18168 hom., cov: 32)

Exomes 𝑓: 0.49 ( 136003 hom. )

Consequence

SERPINA6
NM_001756.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.09

Publications

7 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4 link	c.614-98G>T		intron_variant	Intron 2 of 4	ENST00000341584.4	NP_001747.3	P08185A0A2Z4LCH4
SERPINA6	XM_047431827.1 link	c.763-76G>T		intron_variant	Intron 2 of 4		XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4 link	c.614-98G>T		intron_variant	Intron 2 of 4	1	NM_001756.4	ENSP00000342850.3		P08185
SERPINA6	ENST00000555056.1 link	n.763-98G>T		intron_variant	Intron 2 of 4	2		ENSP00000451045.1		G3V350

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71718

AN:

151864

Hom.:

18147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.604

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.927

Gnomad SAS

AF:

0.649

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.480

GnomAD4 exome

AF:

0.486

AC:

530469

AN:

1090480

Hom.:

136003

AF XY:

0.492

AC XY:

272454

AN XY:

553420

show subpopulations

African (AFR)

AF:

0.357

AC:

9285

AN:

25972

American (AMR)

AF:

0.686

AC:

25126

AN:

36602

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

9130

AN:

23400

East Asian (EAS)

AF:

0.901

AC:

31895

AN:

35404

South Asian (SAS)

AF:

0.624

AC:

46560

AN:

74612

European-Finnish (FIN)

AF:

0.483

AC:

21806

AN:

45116

Middle Eastern (MID)

AF:

0.506

AC:

2131

AN:

4208

European-Non Finnish (NFE)

AF:

0.453

AC:

360778

AN:

797090

Other (OTH)

AF:

0.494

AC:

23758

AN:

48076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

13861

27723

41584

55446

69307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9578

19156

28734

38312

47890

<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:

0.472

AC:

71773

AN:

151982

Hom.:

18168

Cov.:

AF XY:

0.485

AC XY:

36041

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.367

AC:

15223

AN:

41444

American (AMR)

AF:

0.605

AC:

9246

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

1342

AN:

3466

East Asian (EAS)

AF:

0.927

AC:

4777

AN:

5152

South Asian (SAS)

AF:

0.649

AC:

3126

AN:

4820

European-Finnish (FIN)

AF:

0.500

AC:

5287

AN:

10578

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.459

AC:

31160

AN:

67926

Other (OTH)

AF:

0.484

AC:

1020

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1842

3685

5527

7370

9212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.462

Hom.:

46615

Bravo

AF:

0.475

Asia WGS

AF:

0.762

AC:

2646

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.14

(source)

DANN

Benign

0.40

PhyloP100

-2.1

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