10-73375688-C-T

Variant names:

• chr10-73375688-C-T
• rs6896
• NM_001156.5:c.*407G>A

Variant summary

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

The NM_004034.4(ANXA7):​c.*407G>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 0.959 in 152,966 control chromosomes in the GnomAD database, including 70,339 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 0.96 (69997 hom., cov: 30)
  • Exomes 𝑓: 0.95 (342 hom.)
• Consequence: ANXA7 NM_004034.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 9 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]

ENSG00000233144 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 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.*407G>A		3_prime_UTR	Exon 13 of 13	NP_001147.1
	ANXA7	NM_004034.4		c.*407G>A		3_prime_UTR	Exon 14 of 14	NP_004025.1
	ANXA7	NM_001320880.2		c.*407G>A		3_prime_UTR	Exon 13 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.*407G>A		3_prime_UTR	Exon 13 of 13	ENSP00000362012.4
	ANXA7	ENST00000372919.8	TSL:1	c.*407G>A		3_prime_UTR	Exon 14 of 14	ENSP00000362010.4
	ANXA7	ENST00000961271.1		c.*407G>A		3_prime_UTR	Exon 14 of 14	ENSP00000631330.1

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145789 AN: 152100 Hom.: 69937 Cov.: 30

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.947

GnomAD4 exome AF: 0.955 AC: 714 AN: 748 Hom.: 342 Cov.: 0 AF XY: 0.964 AC XY: 401 AN XY: 416

African (AFR) AF: 1.00 AC: 36 AN: 36

American (AMR) AF: 1.00 AC: 14 AN: 14

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 38 AN: 38

East Asian (EAS) AF: 1.00 AC: 30 AN: 30

South Asian (SAS) AF: 1.00 AC: 8 AN: 8

European-Finnish (FIN) AF: 1.00 AC: 38 AN: 38

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.941 AC: 508 AN: 540

Other (OTH) AF: 0.955 AC: 42 AN: 44

GnomAD4 genome AF: 0.959 AC: 145908 AN: 152218 Hom.: 69997 Cov.: 30 AF XY: 0.960 AC XY: 71411 AN XY: 74418

African (AFR) AF: 0.990 AC: 41129 AN: 41534

American (AMR) AF: 0.960 AC: 14667 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 3290 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5174

South Asian (SAS) AF: 0.992 AC: 4789 AN: 4830

European-Finnish (FIN) AF: 0.937 AC: 9921 AN: 10584

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.939 AC: 63882 AN: 68030

Other (OTH) AF: 0.947 AC: 2003 AN: 2114

Alfa AF: 0.943 Hom.: 94277

Bravo AF: 0.962

Asia WGS AF: 0.993 AC: 3443 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		0.088
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: rs6896; hg19: chr10-75135446;