3-38453368-T-C

Variant names:

• chr3-38453368-T-C
• rs1468077
• ENST00000441531.1:n.319-143A>G

Variant summary

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

The ENST00000441531.1(ACVR2B-AS1):​n.319-143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 152,240 control chromosomes in the GnomAD database, including 148 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 0.024 (148 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (0 hom.)
• Consequence: ACVR2B-AS1 ENST00000441531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 1 publications found

Genes affected

ACVR2B-AS1 (HGNC:44161): (ACVR2B antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR2B-AS1	NR_028389.1	n.319-143A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR2B-AS1	ENST00000441531.1	n.319-143A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3624 AN: 151994 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000868

Gnomad OTH AF: 0.0273

GnomAD4 exome AF: 0.00781 AC: 1 AN: 128 Hom.: 0 AF XY: 0.00909 AC XY: 1 AN XY: 110

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 100

Other (OTH) AF: 0.00 AC: 0 AN: 12

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0239 AC: 3640 AN: 152112 Hom.: 148 Cov.: 32 AF XY: 0.0246 AC XY: 1831 AN XY: 74384

African (AFR) AF: 0.0425 AC: 1763 AN: 41510

American (AMR) AF: 0.0473 AC: 723 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.165 AC: 846 AN: 5128

South Asian (SAS) AF: 0.0382 AC: 184 AN: 4820

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10600

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000868 AC: 59 AN: 67970

Other (OTH) AF: 0.0275 AC: 58 AN: 2112

Alfa AF: 0.0115 Hom.: 71

Bravo AF: 0.0301

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.77
PhyloP100		0.023

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1468077; hg19: chr3-38494859;