4-99292276-A-G

Variant names:

• chr4-99292276-A-G
• rs1229966
• ENST00000500358.6:n.4160+1328A>G

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.4160+1328A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,124 control chromosomes in the GnomAD database, including 17,766 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 0.46 (17766 hom., cov: 32)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 15 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 = 0.775 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000500358.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100507053	NR_037884.1		n.4160+1328A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.4160+1328A>G		intron	N/A
	ENSG00000246090	ENST00000509939.1	TSL:3	n.70+1271A>G		intron	N/A
	ENSG00000246090	ENST00000661393.1		n.1268+1271A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69454 AN: 152006 Hom.: 17740 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.457 AC: 69508 AN: 152124 Hom.: 17766 Cov.: 32 AF XY: 0.455 AC XY: 33837 AN XY: 74356

African (AFR) AF: 0.667 AC: 27699 AN: 41498

American (AMR) AF: 0.315 AC: 4810 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1124 AN: 3470

East Asian (EAS) AF: 0.795 AC: 4118 AN: 5180

South Asian (SAS) AF: 0.541 AC: 2606 AN: 4820

European-Finnish (FIN) AF: 0.307 AC: 3247 AN: 10576

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24519 AN: 67976

Other (OTH) AF: 0.420 AC: 888 AN: 2114

Alfa AF: 0.392 Hom.: 16813

Bravo AF: 0.466

Asia WGS AF: 0.544 AC: 1887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.64
PhyloP100		-0.066

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1229966;

hg19: chr4-100213433;