rs11631777

Variant names:

• chr15-60392977-G-A
• rs11631777
• NM_004039.3:c.-12+4966C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-60392977-G-A
• chr15-60392977-G-T

Variant summary

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

The NM_004039.3(ANXA2):​c.-12+4966C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,201,658 control chromosomes in the GnomAD database, including 21,592 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 0.16 (2205 hom., cov: 31)
  • Exomes 𝑓: 0.19 (19387 hom.)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935
• Publications: 9 publications found

Genes affected

ANXA2 (HGNC:537): (annexin A2) This gene encodes a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. This protein functions as an autocrine factor which heightens osteoclast formation and bone resorption. This gene has three pseudogenes located on chromosomes 4, 9 and 10, respectively. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. Annexin A2 expression has been found to correlate with resistance to treatment against various cancer forms. [provided by RefSeq, Dec 2019]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA2	NM_004039.3	c.-12+4966C>T		intron_variant	Intron 1 of 12	ENST00000451270.7	NP_004030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA2	ENST00000451270.7	c.-12+4966C>T		intron_variant	Intron 1 of 12	1	NM_004039.3	ENSP00000387545.3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24776 AN: 151322 Hom.: 2207 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.189 AC: 198473 AN: 1050244 Hom.: 19387 AF XY: 0.190 AC XY: 97073 AN XY: 511236

African (AFR) AF: 0.104 AC: 2150 AN: 20662

American (AMR) AF: 0.147 AC: 2242 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 2615 AN: 11812

East Asian (EAS) AF: 0.0686 AC: 788 AN: 11488

South Asian (SAS) AF: 0.200 AC: 12098 AN: 60362

European-Finnish (FIN) AF: 0.180 AC: 1809 AN: 10046

Middle Eastern (MID) AF: 0.252 AC: 991 AN: 3930

European-Non Finnish (NFE) AF: 0.192 AC: 168955 AN: 878956

Other (OTH) AF: 0.181 AC: 6825 AN: 37760

GnomAD4 genome AF: 0.164 AC: 24772 AN: 151414 Hom.: 2205 Cov.: 31 AF XY: 0.163 AC XY: 12057 AN XY: 73900

African (AFR) AF: 0.112 AC: 4600 AN: 41176

American (AMR) AF: 0.161 AC: 2458 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3472

East Asian (EAS) AF: 0.0717 AC: 371 AN: 5174

South Asian (SAS) AF: 0.191 AC: 915 AN: 4794

European-Finnish (FIN) AF: 0.183 AC: 1889 AN: 10314

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.192 AC: 13015 AN: 67938

Other (OTH) AF: 0.178 AC: 375 AN: 2108

Alfa AF: 0.186 Hom.: 5115

Bravo AF: 0.160

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.27
DANN	Benign	0.32
PhyloP100		-0.94
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: rs11631777; hg19: chr15-60685176;