22-40678403-G-C

Variant names:

• chr22-40678403-G-C
• rs133068
• ENST00000688408.3:n.375+2205C>G

Variant summary

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

The ENST00000688408.3(ENSG00000289292):​n.375+2205C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 149,318 control chromosomes in the GnomAD database, including 31,519 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 0.64 (31519 hom., cov: 26)
• Consequence: ENSG00000289292 ENST00000688408.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• Publications: 4 publications found

Genes affected

ENSG00000289292 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000688408.3. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289292	ENST00000688408.3		n.375+2205C>G		intron	N/A
	ENSG00000289292	ENST00000764106.1		n.197+6340C>G		intron	N/A
	ENSG00000289292	ENST00000764107.1		n.343+2205C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.641 AC: 95698 AN: 149204 Hom.: 31482 Cov.: 26

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.641 AC: 95781 AN: 149318 Hom.: 31519 Cov.: 26 AF XY: 0.639 AC XY: 46391 AN XY: 72574

African (AFR) AF: 0.712 AC: 28795 AN: 40438

American (AMR) AF: 0.491 AC: 7326 AN: 14922

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2178 AN: 3452

East Asian (EAS) AF: 0.976 AC: 4894 AN: 5012

South Asian (SAS) AF: 0.468 AC: 2222 AN: 4746

European-Finnish (FIN) AF: 0.651 AC: 6400 AN: 9826

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.620 AC: 41925 AN: 67644

Other (OTH) AF: 0.637 AC: 1327 AN: 2082

Alfa AF: 0.529 Hom.: 1645

Bravo AF: 0.636

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.48
PhyloP100		-2.8

Splicing

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

Other links and lift over

dbSNP: rs133068; hg19: chr22-41074407;