rs2234965

Variant names:

• chr10-73388358-A-G
• rs2234965
• NM_001156.5:c.492T>C

Variant summary

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

The NM_004034.4(ANXA7):​c.558T>C​(p.Asp186Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.0826 in 1,613,460 control chromosomes in the GnomAD database, including 8,292 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 0.10 (1201 hom., cov: 32)
  • Exomes 𝑓: 0.080 (7091 hom.)
• Consequence: ANXA7 NM_004034.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79
• Publications: 24 publications found

Genes affected

ANXA7 (HGNC:545): (annexin A7) Annexin VII is a member of the annexin family of calcium-dependent phospholipid binding proteins.The Annexin VII gene contains 14 exons and spans approximately 34 kb of DNA. An alternatively spliced cassette exon results in two mRNA transcripts of 2.0 and 2.4 kb which are predicted to generate two protein isoforms differing in their N-terminal domain. The alternative splicing event is tissue specific and the mRNA containing the cassette exon is prevalent in brain, heart and skeletal muscle. The transcripts also differ in their 3'-non coding regions by the use of two alternative poly(A) signals. Annexin VII encodes a protein with a molecular weight of approximately 51 kDa with a unique, highly hydrophobic N-terminal domain of 167 amino acids and a conserved C-terminal region of 299 amino acids. The latter domain is composed of alternating hydrophobic and hydrophilic segments. Structural analysis of the protein suggests that Annexin VII is a membrane binding protein with diverse properties, including voltage-sensitive calcium channel activity, ion selectivity and membrane fusion. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004034.4. 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
	ANXA7	NM_001156.5	MANE Select	c.492T>C	p.Asp164Asp	synonymous	Exon 6 of 13	NP_001147.1
	ANXA7	NM_004034.4		c.558T>C	p.Asp186Asp	synonymous	Exon 7 of 14	NP_004025.1
	ANXA7	NM_001320880.2		c.438T>C	p.Asp146Asp	synonymous	Exon 6 of 13	NP_001307809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA7	ENST00000372921.10	TSL:1 MANE Select	c.492T>C	p.Asp164Asp	synonymous	Exon 6 of 13	ENSP00000362012.4
	ANXA7	ENST00000372919.8	TSL:1	c.558T>C	p.Asp186Asp	synonymous	Exon 7 of 14	ENSP00000362010.4
	ANXA7	ENST00000961271.1		c.582T>C	p.Asp194Asp	synonymous	Exon 7 of 14	ENSP00000631330.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15845 AN: 152100 Hom.: 1181 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0844

Gnomad ASJ AF: 0.0987

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.0436

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0603

Gnomad OTH AF: 0.0936

GnomAD2 exomes AF: 0.109 AC: 27377 AN: 251356 AF XY: 0.112

Gnomad AFR exome AF: 0.162

Gnomad AMR exome AF: 0.0851

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.301

Gnomad FIN exome AF: 0.0453

Gnomad NFE exome AF: 0.0609

Gnomad OTH exome AF: 0.0840

GnomAD4 exome AF: 0.0804 AC: 117422 AN: 1461242 Hom.: 7091 Cov.: 31 AF XY: 0.0841 AC XY: 61150 AN XY: 726902

African (AFR) AF: 0.165 AC: 5515 AN: 33470

American (AMR) AF: 0.0854 AC: 3817 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2683 AN: 26114

East Asian (EAS) AF: 0.285 AC: 11314 AN: 39672

South Asian (SAS) AF: 0.218 AC: 18763 AN: 86144

European-Finnish (FIN) AF: 0.0467 AC: 2495 AN: 53400

Middle Eastern (MID) AF: 0.0688 AC: 397 AN: 5768

European-Non Finnish (NFE) AF: 0.0602 AC: 66864 AN: 1111598

Other (OTH) AF: 0.0923 AC: 5574 AN: 60366

GnomAD4 genome AF: 0.105 AC: 15915 AN: 152218 Hom.: 1201 Cov.: 32 AF XY: 0.107 AC XY: 7962 AN XY: 74424

African (AFR) AF: 0.163 AC: 6784 AN: 41520

American (AMR) AF: 0.0844 AC: 1290 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0987 AC: 342 AN: 3466

East Asian (EAS) AF: 0.299 AC: 1548 AN: 5178

South Asian (SAS) AF: 0.223 AC: 1075 AN: 4822

European-Finnish (FIN) AF: 0.0436 AC: 463 AN: 10616

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0603 AC: 4101 AN: 68016

Other (OTH) AF: 0.0964 AC: 204 AN: 2116

Alfa AF: 0.0748 Hom.: 802

Bravo AF: 0.108

Asia WGS AF: 0.254 AC: 883 AN: 3478

EpiCase AF: 0.0590

EpiControl AF: 0.0587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.8
DANN	Benign	0.82
PhyloP100		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs2234965; hg19: chr10-75148116; COSMIC: COSV65823008; COSMIC: COSV65823008;