rs2071214

Variant names:

• chr17-78223510-G-A
• rs2071214
• NM_001168.3:c.385G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-78223510-G-A
• chr17-78223510-G-C
• chr17-78223510-G-T

Variant summary

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

The NM_001168.3(BIRC5):​c.385G>A​(p.Glu129Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 1,610,428 control chromosomes in the GnomAD database, including 713,948 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.95 (69344 hom., cov: 33)
  • Exomes 𝑓: 0.94 (644604 hom.)
• Consequence: BIRC5 NM_001168.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 59 publications found

Genes affected

BIRC5 (HGNC:593): (baculoviral IAP repeat containing 5) This gene is a member of the inhibitor of apoptosis (IAP) gene family, which encode negative regulatory proteins that prevent apoptotic cell death. IAP family members usually contain multiple baculovirus IAP repeat (BIR) domains, but this gene encodes proteins with only a single BIR domain. The encoded proteins also lack a C-terminus RING finger domain. Gene expression is high during fetal development and in most tumors, yet low in adult tissues. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

ENSG00000308650 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=7.106069E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIRC5	NM_001168.3	c.385G>A	p.Glu129Lys	missense_variant	Exon 4 of 4	ENST00000350051.8	NP_001159.2
BIRC5	NM_001012271.2	c.454G>A	p.Glu152Lys	missense_variant	Exon 5 of 5		NP_001012271.1
BIRC5	NM_001012270.2	c.267G>A	p.Arg89Arg	synonymous_variant	Exon 3 of 3		NP_001012270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIRC5	ENST00000350051.8	c.385G>A	p.Glu129Lys	missense_variant	Exon 4 of 4	1	NM_001168.3	ENSP00000324180.4

Frequencies

GnomAD3 genomes AF: 0.953 AC: 145127 AN: 152220 Hom.: 69282 Cov.: 33

Gnomad AFR AF: 0.988

Gnomad AMI AF: 0.993

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.949

GnomAD2 exomes AF: 0.934 AC: 232374 AN: 248764 AF XY: 0.936

Gnomad AFR exome AF: 0.991

Gnomad AMR exome AF: 0.917

Gnomad ASJ exome AF: 0.952

Gnomad EAS exome AF: 0.788

Gnomad FIN exome AF: 0.934

Gnomad NFE exome AF: 0.948

Gnomad OTH exome AF: 0.948

GnomAD4 exome AF: 0.940 AC: 1370317 AN: 1458090 Hom.: 644604 Cov.: 60 AF XY: 0.940 AC XY: 681727 AN XY: 724946

African (AFR) AF: 0.991 AC: 33021 AN: 33316

American (AMR) AF: 0.918 AC: 40426 AN: 44016

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 24910 AN: 26086

East Asian (EAS) AF: 0.777 AC: 30730 AN: 39564

South Asian (SAS) AF: 0.952 AC: 81470 AN: 85566

European-Finnish (FIN) AF: 0.934 AC: 49838 AN: 53368

Middle Eastern (MID) AF: 0.942 AC: 5417 AN: 5748

European-Non Finnish (NFE) AF: 0.944 AC: 1047761 AN: 1110176

Other (OTH) AF: 0.942 AC: 56744 AN: 60250

GnomAD4 genome AF: 0.953 AC: 145251 AN: 152338 Hom.: 69344 Cov.: 33 AF XY: 0.951 AC XY: 70837 AN XY: 74480

African (AFR) AF: 0.988 AC: 41113 AN: 41596

American (AMR) AF: 0.946 AC: 14476 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 3327 AN: 3472

East Asian (EAS) AF: 0.793 AC: 4104 AN: 5176

South Asian (SAS) AF: 0.953 AC: 4593 AN: 4820

European-Finnish (FIN) AF: 0.932 AC: 9900 AN: 10620

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.949 AC: 64546 AN: 68038

Other (OTH) AF: 0.949 AC: 2007 AN: 2114

Alfa AF: 0.948 Hom.: 232910

Bravo AF: 0.952

TwinsUK AF: 0.939 AC: 3482

ALSPAC AF: 0.943 AC: 3633

ESP6500AA AF: 0.990 AC: 4364

ESP6500EA AF: 0.953 AC: 8198

ExAC AF: 0.936 AC: 113629

Asia WGS AF: 0.911 AC: 3168 AN: 3478

EpiCase AF: 0.956

EpiControl AF: 0.955

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.76
DANN	Benign	0.78
DEOGEN2	Benign	0.0095	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.11	T;T
MetaRNN	Benign	7.1e-7	T;T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.14
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.67	N;N
REVEL	Benign	0.013
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.036
MPC		0.36
ClinPred		0.00063	T
GERP RS		0.41
gMVP		0.43
Mutation Taster		=97/3	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: rs2071214; hg19: chr17-76219591; COSMIC: COSV106097921; COSMIC: COSV106097921;