4-99122354-T-G

Variant names:

• chr4-99122354-T-G
• rs2851253
• ENST00000500358.6:n.429-11201T>G

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.429-11201T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,114 control chromosomes in the GnomAD database, including 48,075 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 0.79 (48075 hom., cov: 32)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.739
• Publications: 9 publications found

Genes affected

ENSG00000246090 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.429-11201T>G		intron_variant	Intron 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000246090	ENST00000500358.6	n.429-11201T>G		intron_variant	Intron 1 of 9	1
ENSG00000246090	ENST00000661393.1	n.426-11201T>G		intron_variant	Intron 1 of 9
ENSG00000246090	ENST00000670724.2	n.481-11201T>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119977 AN: 151996 Hom.: 48021 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.789 AC: 120092 AN: 152114 Hom.: 48075 Cov.: 32 AF XY: 0.797 AC XY: 59262 AN XY: 74354

African (AFR) AF: 0.891 AC: 36988 AN: 41522

American (AMR) AF: 0.792 AC: 12087 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2433 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5175 AN: 5184

South Asian (SAS) AF: 0.884 AC: 4268 AN: 4828

European-Finnish (FIN) AF: 0.766 AC: 8098 AN: 10568

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48607 AN: 67960

Other (OTH) AF: 0.762 AC: 1610 AN: 2112

Alfa AF: 0.739 Hom.: 54954

Bravo AF: 0.796

Asia WGS AF: 0.932 AC: 3239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.8
DANN	Benign	0.76
PhyloP100		0.74

Splicing

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

Other links and lift over

dbSNP: rs2851253; hg19: chr4-100043505;