chr4-79929167-T-C

Variant names:

• chr4-79929167-T-C
• rs4690127
• NM_058172.6:c.1429-21700A>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.1429-21700A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,156 control chromosomes in the GnomAD database, including 2,475 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 0.12 (2475 hom., cov: 32)
• Consequence: ANTXR2 NM_058172.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANTXR2	NM_058172.6	c.1429-21700A>G		intron_variant	Intron 16 of 16	ENST00000403729.7	NP_477520.2
ANTXR2	NM_001286780.2	c.1198-21700A>G		intron_variant	Intron 16 of 16		NP_001273709.1
ANTXR2	NM_001286781.2	c.1198-21700A>G		intron_variant	Intron 16 of 16		NP_001273710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANTXR2	ENST00000403729.7	c.1429-21700A>G		intron_variant	Intron 16 of 16	1	NM_058172.6	ENSP00000385575.2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18271 AN: 152038 Hom.: 2469 Cov.: 32

Gnomad AFR AF: 0.0690

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0687

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.120 AC: 18288 AN: 152156 Hom.: 2475 Cov.: 32 AF XY: 0.134 AC XY: 9992 AN XY: 74366

African (AFR) AF: 0.0690 AC: 2863 AN: 41520

American (AMR) AF: 0.232 AC: 3547 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3470

East Asian (EAS) AF: 0.714 AC: 3687 AN: 5164

South Asian (SAS) AF: 0.318 AC: 1528 AN: 4804

European-Finnish (FIN) AF: 0.142 AC: 1500 AN: 10590

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0688 AC: 4676 AN: 68012

Other (OTH) AF: 0.112 AC: 236 AN: 2116

Alfa AF: 0.0713 Hom.: 202

Bravo AF: 0.126

Asia WGS AF: 0.458 AC: 1588 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.72
PhyloP100		0.13
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: rs4690127; hg19: chr4-80850321;