chr5-151125955-T-C

Variant names:

• chr5-151125955-T-C
• rs10037814
• NM_001155.5:c.1056+447A>G

Variant summary

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

The NM_001155.5(ANXA6):​c.1056+447A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,078 control chromosomes in the GnomAD database, including 17,231 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 0.47 (17231 hom., cov: 32)
• Consequence: ANXA6 NM_001155.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA6	NM_001155.5	c.1056+447A>G		intron_variant	Intron 14 of 25	ENST00000354546.10	NP_001146.2
ANXA6	NM_001363114.2	c.1056+447A>G		intron_variant	Intron 14 of 24		NP_001350043.1
ANXA6	NM_001193544.2	c.960+447A>G		intron_variant	Intron 13 of 24		NP_001180473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA6	ENST00000354546.10	c.1056+447A>G		intron_variant	Intron 14 of 25	1	NM_001155.5	ENSP00000346550.5

Frequencies

GnomAD3 genomes AF: 0.467 AC: 71025 AN: 151960 Hom.: 17215 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.466

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.467 AC: 71090 AN: 152078 Hom.: 17231 Cov.: 32 AF XY: 0.471 AC XY: 35029 AN XY: 74354

African (AFR) AF: 0.514 AC: 21308 AN: 41488

American (AMR) AF: 0.590 AC: 9023 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1532 AN: 3470

East Asian (EAS) AF: 0.738 AC: 3815 AN: 5168

South Asian (SAS) AF: 0.559 AC: 2693 AN: 4818

European-Finnish (FIN) AF: 0.381 AC: 4037 AN: 10592

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27320 AN: 67946

Other (OTH) AF: 0.470 AC: 989 AN: 2106

Alfa AF: 0.435 Hom.: 38427

Bravo AF: 0.485

Asia WGS AF: 0.617 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-0.89
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

Other links and lift over

dbSNP: rs10037814; hg19: chr5-150505516; COSMIC: COSV62906011; COSMIC: COSV62906011;