chr4-99089122-C-G

Position:

• chr4-99089122-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000500358.6(ENSG00000246090):​n.266C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 189,386 control chromosomes in the GnomAD database, including 167 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 0.032 (129 hom., cov: 32)
  • Exomes 𝑓: 0.034 (38 hom.)
• Consequence: ENSG00000246090 ENST00000500358.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

Genes affected

ENSG00000246090 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.032 (4880/152304) while in subpopulation NFE AF= 0.0508 (3458/68024). AF 95% confidence interval is 0.0494. There are 129 homozygotes in gnomad4. There are 2355 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 129 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.266C>G		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000246090	ENST00000500358.6	n.266C>G		non_coding_transcript_exon_variant	1/10	1
ENSG00000246090	ENST00000499178.2	n.172C>G		non_coding_transcript_exon_variant	1/3	3
ENSG00000246090	ENST00000661393.1	n.263C>G		non_coding_transcript_exon_variant	1/10

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4880 AN: 152186 Hom.: 129 Cov.: 32

Gnomad AFR AF: 0.00900

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.0277

GnomAD4 exome AF: 0.0339 AC: 1258 AN: 37082 Hom.: 38 Cov.: 0 AF XY: 0.0328 AC XY: 636 AN XY: 19394

Gnomad4 AFR exome AF: 0.00435

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.0156

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0164

Gnomad4 FIN exome AF: 0.0482

Gnomad4 NFE exome AF: 0.0425

Gnomad4 OTH exome AF: 0.0345

GnomAD4 genome AF: 0.0320 AC: 4880 AN: 152304 Hom.: 129 Cov.: 32 AF XY: 0.0316 AC XY: 2355 AN XY: 74476

Gnomad4 AFR AF: 0.00897

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0155

Gnomad4 FIN AF: 0.0537

Gnomad4 NFE AF: 0.0508

Gnomad4 OTH AF: 0.0274

Alfa AF: 0.0477 Hom.: 28

Bravo AF: 0.0281

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17216887; hg19: chr4-100010273;