4-99103577-C-G

Variant names:

• chr4-99103577-C-G
• rs1869458
• ENST00000500358.6:n.428+14293C>G

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.428+14293C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,052 control chromosomes in the GnomAD database, including 10,329 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 0.34 (10329 hom., cov: 32)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.494 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.428+14293C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.428+14293C>G		intron	N/A
	ENSG00000246090	ENST00000661393.1		n.425+14293C>G		intron	N/A
	ENSG00000246090	ENST00000670724.2		n.480+14293C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51363 AN: 151934 Hom.: 10324 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.338 AC: 51367 AN: 152052 Hom.: 10329 Cov.: 32 AF XY: 0.341 AC XY: 25317 AN XY: 74308

African (AFR) AF: 0.134 AC: 5570 AN: 41520

American (AMR) AF: 0.329 AC: 5028 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3472

East Asian (EAS) AF: 0.129 AC: 668 AN: 5184

South Asian (SAS) AF: 0.510 AC: 2456 AN: 4812

European-Finnish (FIN) AF: 0.453 AC: 4770 AN: 10534

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30282 AN: 67938

Other (OTH) AF: 0.354 AC: 747 AN: 2112

Alfa AF: 0.384 Hom.: 1524

Bravo AF: 0.313

Asia WGS AF: 0.374 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.8
DANN	Benign	0.67
PhyloP100		-1.4

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: rs1869458;

hg19: chr4-100024728;