chr14-94309400-A-G

Variant names:

• chr14-94309400-A-G
• rs11622970
• NM_001756.4:c.884+336T>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.884+336T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,092 control chromosomes in the GnomAD database, including 18,460 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 0.48 (18460 hom., cov: 32)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789
• Publications: 2 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=-0.99).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA6	NM_001756.4	MANE Select	c.884+336T>C		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.884+336T>C		intron	N/A	ENSP00000342850.3
	SERPINA6	ENST00000555056.1	TSL:2	n.*196+336T>C		intron	N/A	ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72464 AN: 151974 Hom.: 18433 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.477 AC: 72529 AN: 152092 Hom.: 18460 Cov.: 32 AF XY: 0.489 AC XY: 36384 AN XY: 74340

African (AFR) AF: 0.384 AC: 15927 AN: 41476

American (AMR) AF: 0.606 AC: 9264 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3468

East Asian (EAS) AF: 0.927 AC: 4791 AN: 5170

South Asian (SAS) AF: 0.650 AC: 3132 AN: 4822

European-Finnish (FIN) AF: 0.498 AC: 5255 AN: 10560

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31200 AN: 68002

Other (OTH) AF: 0.485 AC: 1023 AN: 2110

Alfa AF: 0.452 Hom.: 3305

Bravo AF: 0.481

Asia WGS AF: 0.764 AC: 2652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		-0.79
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: rs11622970; hg19: chr14-94775737;