4-99221145-C-T

Variant names:

• chr4-99221145-C-T
• rs10008281
• ENST00000500358.6:n.3789+16714C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000500358.6(ENSG00000246090):​n.3789+16714C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 152,028 control chromosomes in the GnomAD database, including 3 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 0.0012 (3 hom., cov: 32)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799
• Publications: 12 publications found

Genes affected

ENSG00000246090 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BS2: High Homozygotes in GnomAd4 at 3 gene

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.3789+16714C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3789+16714C>T		intron	N/A
	ENSG00000246090	ENST00000506160.1	TSL:4	n.407+16714C>T		intron	N/A
	ENSG00000246090	ENST00000506454.2	TSL:3	n.168+16718C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 186 AN: 151912 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000379

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00184

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00122 AC: 186 AN: 152028 Hom.: 3 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74336

African (AFR) AF: 0.000386 AC: 16 AN: 41462

American (AMR) AF: 0.000328 AC: 5 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.000379 AC: 4 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00184 AC: 125 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000494 Hom.: 6160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.8
DANN	Benign	0.50
PhyloP100		-0.80

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: rs10008281;

hg19: chr4-100142302;