NM_058172.6:c.-82C>A

Variant names:

• chr4-80072642-G-T
• rs13140055
• NM_058172.6:c.-82C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_058172.6(ANTXR2):​c.-82C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,359,096 control chromosomes in the GnomAD database, including 102,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11501 hom., cov: 31)
  • Exomes 𝑓: 0.38 (91049 hom.)
• Consequence: ANTXR2 NM_058172.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.333
• Publications: 15 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: ClinGen, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 4-80072642-G-T is Benign according to our data. Variant chr4-80072642-G-T is described in ClinVar as Benign. ClinVar VariationId is 349890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058172.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR2	NM_058172.6	MANE Select	c.-82C>A		5_prime_UTR	Exon 1 of 17	NP_477520.2	P58335-4
	ANTXR2	NM_001145794.2		c.-82C>A		5_prime_UTR	Exon 1 of 16	NP_001139266.1	P58335-1
	ANTXR2	NM_001286780.2		c.-80+753C>A		intron	N/A	NP_001273709.1	J3KPY9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR2	ENST00000403729.7	TSL:1 MANE Select	c.-82C>A		5_prime_UTR	Exon 1 of 17	ENSP00000385575.2	P58335-4
	ANTXR2	ENST00000346652.10	TSL:1	c.-82C>A		5_prime_UTR	Exon 1 of 12	ENSP00000314883.6	P58335-2
	ANTXR2	ENST00000404191.5	TSL:1	c.-80+753C>A		intron	N/A	ENSP00000384028.1	J3KPY9

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58356 AN: 151652 Hom.: 11489 Cov.: 31

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.384 AC: 463464 AN: 1207324 Hom.: 91049 Cov.: 33 AF XY: 0.389 AC XY: 226153 AN XY: 581580

African (AFR) AF: 0.450 AC: 10693 AN: 23784

American (AMR) AF: 0.296 AC: 3573 AN: 12078

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 7072 AN: 17084

East Asian (EAS) AF: 0.209 AC: 5742 AN: 27466

South Asian (SAS) AF: 0.567 AC: 29704 AN: 52388

European-Finnish (FIN) AF: 0.376 AC: 11606 AN: 30858

Middle Eastern (MID) AF: 0.495 AC: 1668 AN: 3370

European-Non Finnish (NFE) AF: 0.377 AC: 373833 AN: 990450

Other (OTH) AF: 0.393 AC: 19573 AN: 49846

GnomAD4 genome AF: 0.385 AC: 58402 AN: 151772 Hom.: 11501 Cov.: 31 AF XY: 0.384 AC XY: 28525 AN XY: 74228

African (AFR) AF: 0.436 AC: 18062 AN: 41422

American (AMR) AF: 0.297 AC: 4539 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1423 AN: 3460

East Asian (EAS) AF: 0.214 AC: 1094 AN: 5116

South Asian (SAS) AF: 0.553 AC: 2660 AN: 4808

European-Finnish (FIN) AF: 0.367 AC: 3875 AN: 10558

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25474 AN: 67842

Other (OTH) AF: 0.378 AC: 794 AN: 2100

Alfa AF: 0.380 Hom.: 10468

Bravo AF: 0.377

Asia WGS AF: 0.363 AC: 1264 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hyaline fibromatosis syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.8
DANN	Benign	0.88
PhyloP100		-0.33
PromoterAI		-0.035	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs13140055; hg19: chr4-80993796;