chr14-94307074-C-T

Variant names:

• chr14-94307074-C-T
• rs2144835
• NM_001756.4:c.885-856G>A

Variant summary

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

The NM_001756.4(SERPINA6):​c.885-856G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,044 control chromosomes in the GnomAD database, including 42,495 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 0.74 (42495 hom., cov: 31)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• Publications: 7 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA6	NM_001756.4	MANE Select	c.885-856G>A		intron	N/A	NP_001747.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA6	ENST00000341584.4	TSL:1 MANE Select	c.885-856G>A		intron	N/A	ENSP00000342850.3
	SERPINA6	ENST00000555056.1	TSL:2	n.*197-856G>A		intron	N/A	ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112678 AN: 151924 Hom.: 42462 Cov.: 31

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.742 AC: 112762 AN: 152044 Hom.: 42495 Cov.: 31 AF XY: 0.740 AC XY: 54976 AN XY: 74304

African (AFR) AF: 0.842 AC: 34926 AN: 41478

American (AMR) AF: 0.639 AC: 9768 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2249 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5138 AN: 5160

South Asian (SAS) AF: 0.732 AC: 3521 AN: 4812

European-Finnish (FIN) AF: 0.736 AC: 7789 AN: 10586

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 46996 AN: 67954

Other (OTH) AF: 0.731 AC: 1539 AN: 2104

Alfa AF: 0.706 Hom.: 23119

Bravo AF: 0.743

Asia WGS AF: 0.863 AC: 3001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.46
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2144835; hg19: chr14-94773411;