rs4389526

Variant names:

• chr4-80025321-T-A
• rs4389526
• NM_058172.6:c.866+6302A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-80025321-T-A
• chr4-80025321-T-C
• chr4-80025321-T-G

Variant summary

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

The NM_058172.6(ANTXR2):​c.866+6302A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,048 control chromosomes in the GnomAD database, including 28,626 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 0.60 (28626 hom., cov: 33)
• Consequence: ANTXR2 NM_058172.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842
• Publications: 22 publications found

Genes affected

ANTXR2 (HGNC:21732): (ANTXR cell adhesion molecule 2) This gene encodes a receptor for anthrax toxin. The protein binds to collagen IV and laminin, suggesting that it may be involved in extracellular matrix adhesion. Mutations in this gene cause juvenile hyaline fibromatosis and infantile systemic hyalinosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ANTXR2 Gene-Disease associations (from GenCC):

• hyaline fibromatosis syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• juvenile hyaline fibromatosis

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• infantile systemic hyalinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANTXR2	NM_058172.6	c.866+6302A>T		intron_variant	Intron 10 of 16	ENST00000403729.7	NP_477520.2
ANTXR2	NM_001145794.2	c.866+6302A>T		intron_variant	Intron 10 of 15		NP_001139266.1
ANTXR2	NM_001286780.2	c.635+6302A>T		intron_variant	Intron 10 of 16		NP_001273709.1
ANTXR2	NM_001286781.2	c.635+6302A>T		intron_variant	Intron 10 of 16		NP_001273710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANTXR2	ENST00000403729.7	c.866+6302A>T		intron_variant	Intron 10 of 16	1	NM_058172.6	ENSP00000385575.2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90536 AN: 151930 Hom.: 28606 Cov.: 33

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.596 AC: 90600 AN: 152048 Hom.: 28626 Cov.: 33 AF XY: 0.607 AC XY: 45089 AN XY: 74292

African (AFR) AF: 0.388 AC: 16083 AN: 41476

American (AMR) AF: 0.730 AC: 11153 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2396 AN: 3472

East Asian (EAS) AF: 0.934 AC: 4829 AN: 5172

South Asian (SAS) AF: 0.772 AC: 3722 AN: 4822

European-Finnish (FIN) AF: 0.676 AC: 7145 AN: 10576

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43274 AN: 67946

Other (OTH) AF: 0.606 AC: 1274 AN: 2104

Alfa AF: 0.612 Hom.: 3693

Bravo AF: 0.589

Asia WGS AF: 0.818 AC: 2823 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.5
DANN	Benign	0.63
PhyloP100		-0.84
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: rs4389526; hg19: chr4-80946475;