rs1042394

Variant names:

• chr14-94306167-G-A
• rs1042394
• NM_001756.4:c.936C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-94306167-G-A
• chr14-94306167-G-C
• chr14-94306167-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001756.4(SERPINA6):​c.936C>T​(p.Leu312Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,613,834 control chromosomes in the GnomAD database, including 54,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (4230 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49860 hom.)
• Consequence: SERPINA6 NM_001756.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.163
• Publications: 14 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, AD, AR, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-94306167-G-A is Benign according to our data. Variant chr14-94306167-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060392.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.163 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 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.936C>T	p.Leu312Leu	synonymous	Exon 4 of 5	NP_001747.3	P08185

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA6	ENST00000341584.4	TSL:1 MANE Select	c.936C>T	p.Leu312Leu	synonymous	Exon 4 of 5	ENSP00000342850.3	P08185
	SERPINA6	ENST00000874318.1		c.1107C>T	p.Leu369Leu	synonymous	Exon 4 of 5	ENSP00000544377.1
	SERPINA6	ENST00000874321.1		c.1029C>T	p.Leu343Leu	synonymous	Exon 5 of 6	ENSP00000544380.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34686 AN: 152022 Hom.: 4227 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.214

GnomAD2 exomes AF: 0.218 AC: 54685 AN: 251288 AF XY: 0.218

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.0605

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.226

GnomAD4 exome AF: 0.255 AC: 373020 AN: 1461694 Hom.: 49860 Cov.: 37 AF XY: 0.252 AC XY: 183490 AN XY: 727156

African (AFR) AF: 0.178 AC: 5973 AN: 33476

American (AMR) AF: 0.147 AC: 6567 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 5311 AN: 26134

East Asian (EAS) AF: 0.0918 AC: 3645 AN: 39700

South Asian (SAS) AF: 0.151 AC: 12986 AN: 86256

European-Finnish (FIN) AF: 0.286 AC: 15287 AN: 53412

Middle Eastern (MID) AF: 0.176 AC: 1012 AN: 5766

European-Non Finnish (NFE) AF: 0.277 AC: 307905 AN: 1111838

Other (OTH) AF: 0.237 AC: 14334 AN: 60390

GnomAD4 genome AF: 0.228 AC: 34689 AN: 152140 Hom.: 4230 Cov.: 32 AF XY: 0.222 AC XY: 16485 AN XY: 74372

African (AFR) AF: 0.184 AC: 7645 AN: 41512

American (AMR) AF: 0.180 AC: 2760 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3470

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

South Asian (SAS) AF: 0.134 AC: 646 AN: 4826

European-Finnish (FIN) AF: 0.278 AC: 2932 AN: 10564

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18878 AN: 67992

Other (OTH) AF: 0.213 AC: 448 AN: 2108

Alfa AF: 0.223 Hom.: 1542

Bravo AF: 0.220

Asia WGS AF: 0.104 AC: 363 AN: 3478

EpiCase AF: 0.269

EpiControl AF: 0.275

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SERPINA6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.82
DANN	Benign	0.57
PhyloP100		-0.16
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: rs1042394; hg19: chr14-94772504; COSMIC: COSV58585344;