4-80028675-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_058172.6(ANTXR2):c.866+2948G>A 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 152,014 control chromosomes in the GnomAD database, including 28,606 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 (28606 hom., cov: 32)
• Consequence: ANTXR2 NM_058172.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• 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/exons	MANE	UniProt
ANTXR2	NM_058172.6	c.866+2948G>A		intron_variant		ENST00000403729.7
ANTXR2	NM_001145794.2	c.866+2948G>A		intron_variant
ANTXR2	NM_001286780.2	c.635+2948G>A		intron_variant
ANTXR2	NM_001286781.2	c.635+2948G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANTXR2	ENST00000403729.7	c.866+2948G>A		intron_variant		1	NM_058172.6	P1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90490 AN: 151896 Hom.: 28586 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.729

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: 0.602

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

GnomAD4 genome AF: 0.596 AC: 90554 AN: 152014 Hom.: 28606 Cov.: 32 AF XY: 0.607 AC XY: 45055 AN XY: 74270

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.934

Gnomad4 SAS AF: 0.772

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.605

Alfa AF: 0.640 Hom.: 60911

Bravo AF: 0.589

Asia WGS AF: 0.818 AC: 2842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	14
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs4333130; hg19: chr4-80949829;