14-94319114-T-C

Variant names:

• chr14-94319114-T-C
• rs11627241
• NM_001756.4:c.-20+4153A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001756.4(SERPINA6):​c.-20+4153A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 151,970 control chromosomes in the GnomAD database, including 39,914 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 0.71 (39914 hom., cov: 31)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• Publications: 8 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.-20+4153A>G		intron_variant	Intron 1 of 4	ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.-20+4153A>G		intron_variant	Intron 1 of 4		XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4	c.-20+4153A>G		intron_variant	Intron 1 of 4	1	NM_001756.4	ENSP00000342850.3
SERPINA6	ENST00000557225.1	c.-188+4153A>G		intron_variant	Intron 1 of 1	2		ENSP00000452018.1
SERPINA6	ENST00000555056.1	n.-20+4153A>G		intron_variant	Intron 1 of 4	2		ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108288 AN: 151850 Hom.: 39884 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.717

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.713 AC: 108370 AN: 151970 Hom.: 39914 Cov.: 31 AF XY: 0.718 AC XY: 53355 AN XY: 74274

African (AFR) AF: 0.534 AC: 22108 AN: 41392

American (AMR) AF: 0.808 AC: 12356 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2197 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5136 AN: 5152

South Asian (SAS) AF: 0.826 AC: 3980 AN: 4820

European-Finnish (FIN) AF: 0.774 AC: 8173 AN: 10562

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.765 AC: 51999 AN: 67972

Other (OTH) AF: 0.719 AC: 1520 AN: 2114

Alfa AF: 0.703 Hom.: 3018

Bravo AF: 0.707

Asia WGS AF: 0.906 AC: 3151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.59
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11627241; hg19: chr14-94785451;