chr5-151100959-C-T

Variant names:

• chr5-151100959-C-T
• rs11960458
• NM_001155.5:c.*489G>A

Variant summary

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

The NM_001155.5(ANXA6):​c.*489G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 456,712 control chromosomes in the GnomAD database, including 12,618 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 0.20 (3452 hom., cov: 32)
  • Exomes 𝑓: 0.23 (9166 hom.)
• Consequence: ANXA6 NM_001155.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 23 publications found

Genes affected

ANXA6 (HGNC:544): (annexin A6) Annexin VI belongs to a family of calcium-dependent membrane and phospholipid binding proteins. Several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. The annexin VI gene is approximately 60 kbp long and contains 26 exons. It encodes a protein of about 68 kDa that consists of eight 68-amino acid repeats separated by linking sequences of variable lengths. It is highly similar to human annexins I and II sequences, each of which contain four such repeats. Annexin VI has been implicated in mediating the endosome aggregation and vesicle fusion in secreting epithelia during exocytosis. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA6	NM_001155.5	c.*489G>A		3_prime_UTR_variant	Exon 26 of 26	ENST00000354546.10	NP_001146.2
ANXA6	NM_001363114.2	c.*489G>A		3_prime_UTR_variant	Exon 25 of 25		NP_001350043.1
ANXA6	NM_001193544.2	c.*489G>A		3_prime_UTR_variant	Exon 25 of 25		NP_001180473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA6	ENST00000354546.10	c.*489G>A		3_prime_UTR_variant	Exon 26 of 26	1	NM_001155.5	ENSP00000346550.5

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29936 AN: 151970 Hom.: 3445 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.198

GnomAD2 exomes AF: 0.263 AC: 33742 AN: 128446 AF XY: 0.247

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.437

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.435

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.228 AC: 69332 AN: 304624 Hom.: 9166 Cov.: 0 AF XY: 0.219 AC XY: 37990 AN XY: 173400

African (AFR) AF: 0.131 AC: 1135 AN: 8654

American (AMR) AF: 0.436 AC: 11903 AN: 27298

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 2634 AN: 10814

East Asian (EAS) AF: 0.433 AC: 4001 AN: 9242

South Asian (SAS) AF: 0.196 AC: 11696 AN: 59744

European-Finnish (FIN) AF: 0.209 AC: 2587 AN: 12390

Middle Eastern (MID) AF: 0.281 AC: 782 AN: 2784

European-Non Finnish (NFE) AF: 0.197 AC: 31427 AN: 159428

Other (OTH) AF: 0.222 AC: 3167 AN: 14270

GnomAD4 genome AF: 0.197 AC: 29949 AN: 152088 Hom.: 3452 Cov.: 32 AF XY: 0.202 AC XY: 15046 AN XY: 74360

African (AFR) AF: 0.124 AC: 5154 AN: 41498

American (AMR) AF: 0.323 AC: 4941 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 879 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2151 AN: 5176

South Asian (SAS) AF: 0.190 AC: 916 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2083 AN: 10574

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13169 AN: 67958

Other (OTH) AF: 0.195 AC: 412 AN: 2108

Alfa AF: 0.202 Hom.: 9215

Bravo AF: 0.209

Asia WGS AF: 0.228 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.3
DANN	Benign	0.92
PhyloP100		-0.057

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11960458; hg19: chr5-150480520; COSMIC: COSV62906802;