rs2070777

Variant names:

• chr14-94568005-T-A
• rs2070777
• NM_006215.4:c.924-124T>A

Variant summary

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

The NM_006215.4(SERPINA4):​c.924-124T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 920,980 control chromosomes in the GnomAD database, including 68,632 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 0.41 (13319 hom., cov: 32)
  • Exomes 𝑓: 0.37 (55313 hom.)
• Consequence: SERPINA4 NM_006215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 6 publications found

Genes affected

SERPINA4 (HGNC:8948): (serpin family A member 4) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Located in extracellular exosome. Biomarker of diabetic retinopathy. [provided by Alliance of Genome Resources, Apr 2022]

SERPINA5 (HGNC:8723): (serpin family A member 5) The protein encoded by this gene is a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. This gene is one in a cluster of serpin genes located on the q arm of chromosome 14. This family member is a glycoprotein that can inhibit several serine proteases, including protein C and various plasminogen activators and kallikreins, and it thus plays diverse roles in hemostasis and thrombosis in multiple organs. [provided by RefSeq, Aug 2012]

ENSG00000294537 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006215.4. 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
	SERPINA4	NM_006215.4	MANE Select	c.924-124T>A		intron	N/A	NP_006206.2
	SERPINA4	NM_001289032.2		c.1035-124T>A		intron	N/A	NP_001275961.1
	SERPINA4	NM_001289033.2		c.924-124T>A		intron	N/A	NP_001275962.1	P29622

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA4	ENST00000557004.6	TSL:1 MANE Select	c.924-124T>A		intron	N/A	ENSP00000450838.1	P29622
	SERPINA4	ENST00000298841.5	TSL:1	c.924-124T>A		intron	N/A	ENSP00000298841.5	P29622
	SERPINA4	ENST00000555095.5	TSL:1	c.924-124T>A		intron	N/A	ENSP00000451172.1	P29622

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62559 AN: 151900 Hom.: 13289 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.373 AC: 286951 AN: 768958 Hom.: 55313 AF XY: 0.378 AC XY: 150223 AN XY: 397388

African (AFR) AF: 0.523 AC: 9957 AN: 19046

American (AMR) AF: 0.339 AC: 10371 AN: 30584

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 6537 AN: 16732

East Asian (EAS) AF: 0.427 AC: 15365 AN: 35958

South Asian (SAS) AF: 0.515 AC: 29284 AN: 56860

European-Finnish (FIN) AF: 0.406 AC: 16357 AN: 40290

Middle Eastern (MID) AF: 0.404 AC: 1702 AN: 4214

European-Non Finnish (NFE) AF: 0.346 AC: 183046 AN: 528504

Other (OTH) AF: 0.390 AC: 14332 AN: 36770

GnomAD4 genome AF: 0.412 AC: 62648 AN: 152022 Hom.: 13319 Cov.: 32 AF XY: 0.415 AC XY: 30815 AN XY: 74288

African (AFR) AF: 0.522 AC: 21637 AN: 41466

American (AMR) AF: 0.356 AC: 5439 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1342 AN: 3472

East Asian (EAS) AF: 0.404 AC: 2073 AN: 5130

South Asian (SAS) AF: 0.525 AC: 2529 AN: 4816

European-Finnish (FIN) AF: 0.414 AC: 4378 AN: 10568

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24058 AN: 67968

Other (OTH) AF: 0.426 AC: 899 AN: 2112

Alfa AF: 0.387 Hom.: 1428

Bravo AF: 0.408

Asia WGS AF: 0.497 AC: 1726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.62
DANN	Benign	0.65
PhyloP100		-0.18
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2070777;

hg19: chr14-95034342;