22-28804405-G-A

Variant names:

• chr22-28804405-G-A
• rs35679096
• ENST00000418292.1:n.34+3668G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000418292.1(ENSG00000226471):​n.34+3668G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 151,886 control chromosomes in the GnomAD database, including 53 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 0.021 (53 hom., cov: 30)
• Consequence: ENSG00000226471 ENST00000418292.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 2 publications found

Genes affected

ENSG00000226471 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.021 (3190/151886) while in subpopulation NFE AF = 0.0334 (2270/67950). AF 95% confidence interval is 0.0323. There are 53 homozygotes in GnomAd4. There are 1453 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 53 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000418292.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000226471	ENST00000418292.1	TSL:3	n.34+3668G>A		intron	N/A
	ENSG00000226471	ENST00000451486.5	TSL:5	n.103+2411G>A		intron	N/A
	ENSG00000226471	ENST00000458080.2	TSL:3	n.55+3668G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3190 AN: 151770 Hom.: 53 Cov.: 30

Gnomad AFR AF: 0.00584

Gnomad AMI AF: 0.0573

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0334

Gnomad OTH AF: 0.0221

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

GnomAD4 genome AF: 0.0210 AC: 3190 AN: 151886 Hom.: 53 Cov.: 30 AF XY: 0.0196 AC XY: 1453 AN XY: 74236

African (AFR) AF: 0.00582 AC: 241 AN: 41394

American (AMR) AF: 0.0125 AC: 191 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 72 AN: 3466

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5178

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4816

European-Finnish (FIN) AF: 0.0193 AC: 203 AN: 10536

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0334 AC: 2270 AN: 67950

Other (OTH) AF: 0.0219 AC: 46 AN: 2104

Alfa AF: 0.0251 Hom.: 23

Bravo AF: 0.0192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.21
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs35679096; hg19: chr22-29200393;