rs6116

Variant names:

• chr14-94592125-A-C
• rs6116
• NM_000624.6:c.1107A>C

Your query was ambiguous. Multiple possible variants found:

• chr14-94592125-A-C
• chr14-94592125-A-G
• chr14-94592125-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000329597.12(SERPINA5):​c.1107A>C​(p.Ile369Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,613,828 control chromosomes in the GnomAD database, including 172,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. I369I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.40 (12920 hom., cov: 32)
  • Exomes 𝑓: 0.46 (159379 hom.)
• Consequence: SERPINA5 ENST00000329597.12 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 21 publications found

Genes affected

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]

ENSG00000273259 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.002 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000329597.12. 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
	SERPINA5	NM_000624.6	MANE Select	c.1107A>C	p.Ile369Ile	synonymous	Exon 6 of 6	NP_000615.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA5	ENST00000329597.12	TSL:1 MANE Select	c.1107A>C	p.Ile369Ile	synonymous	Exon 6 of 6	ENSP00000333203.7
	SERPINA5	ENST00000554276.1	TSL:1	c.1107A>C	p.Ile369Ile	synonymous	Exon 5 of 5	ENSP00000451610.1
	ENSG00000273259	ENST00000553947.1	TSL:2	n.66A>C		non_coding_transcript_exon	Exon 1 of 8	ENSP00000452367.2

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60114 AN: 151930 Hom.: 12920 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.0865

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.405

GnomAD2 exomes AF: 0.391 AC: 98140 AN: 251260 AF XY: 0.402

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.535

Gnomad EAS exome AF: 0.0757

Gnomad FIN exome AF: 0.508

Gnomad NFE exome AF: 0.483

Gnomad OTH exome AF: 0.437

GnomAD4 exome AF: 0.457 AC: 668604 AN: 1461778 Hom.: 159379 Cov.: 56 AF XY: 0.457 AC XY: 332018 AN XY: 727184

African (AFR) AF: 0.285 AC: 9537 AN: 33476

American (AMR) AF: 0.226 AC: 10125 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 13893 AN: 26126

East Asian (EAS) AF: 0.0887 AC: 3521 AN: 39700

South Asian (SAS) AF: 0.362 AC: 31218 AN: 86246

European-Finnish (FIN) AF: 0.511 AC: 27307 AN: 53414

Middle Eastern (MID) AF: 0.555 AC: 3200 AN: 5762

European-Non Finnish (NFE) AF: 0.489 AC: 543260 AN: 1111956

Other (OTH) AF: 0.440 AC: 26543 AN: 60388

GnomAD4 genome AF: 0.395 AC: 60123 AN: 152050 Hom.: 12920 Cov.: 32 AF XY: 0.394 AC XY: 29257 AN XY: 74320

African (AFR) AF: 0.287 AC: 11890 AN: 41452

American (AMR) AF: 0.313 AC: 4779 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1859 AN: 3468

East Asian (EAS) AF: 0.0864 AC: 447 AN: 5172

South Asian (SAS) AF: 0.340 AC: 1636 AN: 4812

European-Finnish (FIN) AF: 0.513 AC: 5412 AN: 10558

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32806 AN: 67984

Other (OTH) AF: 0.400 AC: 845 AN: 2112

Alfa AF: 0.446 Hom.: 26716

Bravo AF: 0.374

Asia WGS AF: 0.195 AC: 684 AN: 3478

EpiCase AF: 0.489

EpiControl AF: 0.492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.58
PhyloP100		-0.0020
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6116; hg19: chr14-95058462; COSMIC: COSV61573675; COSMIC: COSV61573675;