9-134525462-G-T

Variant names:

• chr9-134525462-G-T
• rs10776839
• ENST00000745249.1:n.1012-19458G>T

Variant summary

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

The ENST00000745249.1(ENSG00000228877):​n.1012-19458G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,108 control chromosomes in the GnomAD database, including 13,520 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 0.42 (13520 hom., cov: 34)
• Consequence: ENSG00000228877 ENST00000745249.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 16 publications found

Genes affected

ENSG00000228877 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100506532	NR_188441.1	n.184-19458G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000228877	ENST00000745249.1	n.1012-19458G>T		intron_variant	Intron 7 of 7
ENSG00000228877	ENST00000745250.1	n.271-19458G>T		intron_variant	Intron 3 of 3
ENSG00000228877	ENST00000745251.1	n.749-19458G>T		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63563 AN: 151990 Hom.: 13529 Cov.: 34

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.418 AC: 63588 AN: 152108 Hom.: 13520 Cov.: 34 AF XY: 0.417 AC XY: 30985 AN XY: 74338

African (AFR) AF: 0.362 AC: 15005 AN: 41496

American (AMR) AF: 0.476 AC: 7278 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1805 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2252 AN: 5164

South Asian (SAS) AF: 0.361 AC: 1739 AN: 4820

European-Finnish (FIN) AF: 0.383 AC: 4051 AN: 10576

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29955 AN: 67982

Other (OTH) AF: 0.428 AC: 904 AN: 2110

Alfa AF: 0.439 Hom.: 21430

Bravo AF: 0.428

Asia WGS AF: 0.409 AC: 1423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.73
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs10776839; hg19: chr9-137417308;