rs2144834

Variant names:

• chr14-94307297-G-A
• rs2144834
• NM_001756.4:c.885-1079C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-94307297-G-A
• chr14-94307297-G-C

Variant summary

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

The NM_001756.4(SERPINA6):​c.885-1079C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,950 control chromosomes in the GnomAD database, including 3,403 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 (3403 hom., cov: 32)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 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.885-1079C>T		intron	N/A	NP_001747.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA6	ENST00000341584.4	TSL:1 MANE Select	c.885-1079C>T		intron	N/A	ENSP00000342850.3
	SERPINA6	ENST00000874318.1		c.1056-1079C>T		intron	N/A	ENSP00000544377.1
	SERPINA6	ENST00000874321.1		c.885-521C>T		intron	N/A	ENSP00000544380.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31306 AN: 151832 Hom.: 3399 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.206 AC: 31312 AN: 151950 Hom.: 3403 Cov.: 32 AF XY: 0.200 AC XY: 14862 AN XY: 74256

African (AFR) AF: 0.174 AC: 7214 AN: 41438

American (AMR) AF: 0.156 AC: 2385 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3468

East Asian (EAS) AF: 0.0660 AC: 341 AN: 5170

South Asian (SAS) AF: 0.131 AC: 629 AN: 4796

European-Finnish (FIN) AF: 0.242 AC: 2550 AN: 10538

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16839 AN: 67946

Other (OTH) AF: 0.186 AC: 391 AN: 2106

Alfa AF: 0.230 Hom.: 17745

Bravo AF: 0.198

Asia WGS AF: 0.100 AC: 349 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	3.4
DANN	Benign	0.72
PhyloP100		-0.22
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: rs2144834; hg19: chr14-94773634;