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: 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 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.614-98G>T		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.614-98G>T	intron	N/A	ENSP00000342850.3	P08185
SERPINA6	ENST00000874318.1		c.763-76G>T	intron	N/A	ENSP00000544377.1
SERPINA6	ENST00000874321.1		c.614-98G>T	intron	N/A	ENSP00000544380.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over