rs41458646

Variant names:

• chr2-23016071-A-G
• rs41458646
• ENST00000791349.1:n.419-471T>C

Variant summary

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

The ENST00000791349.1(ENSG00000232451):​n.419-471T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,248 control chromosomes in the GnomAD database, including 2,454 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 0.16 (2454 hom., cov: 32)
• Consequence: ENSG00000232451 ENST00000791349.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420
• Publications: 4 publications found

Genes affected

ENSG00000232451 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232451	ENST00000791349.1	n.419-471T>C		intron_variant	Intron 3 of 3
ENSG00000232451	ENST00000791350.1	n.332-471T>C		intron_variant	Intron 2 of 2
ENSG00000232451	ENST00000791351.1	n.430-471T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23908 AN: 152130 Hom.: 2439 Cov.: 32

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.157 AC: 23940 AN: 152248 Hom.: 2454 Cov.: 32 AF XY: 0.165 AC XY: 12246 AN XY: 74426

African (AFR) AF: 0.0410 AC: 1705 AN: 41568

American (AMR) AF: 0.242 AC: 3696 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3470

East Asian (EAS) AF: 0.336 AC: 1738 AN: 5176

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4828

European-Finnish (FIN) AF: 0.225 AC: 2383 AN: 10582

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12052 AN: 68014

Other (OTH) AF: 0.198 AC: 419 AN: 2112

Alfa AF: 0.153 Hom.: 1345

Bravo AF: 0.154

Asia WGS AF: 0.316 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.7
DANN	Benign	0.87
PhyloP100		0.42

Splicing

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

Other links and lift over

dbSNP: rs41458646; hg19: chr2-23238943;