4-117730668-T-C

Variant names:

• chr4-117730668-T-C
• rs4422476
• ENST00000755294.1:n.275+18645A>G

Variant summary

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

The ENST00000755294.1(ENSG00000288921):​n.275+18645A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,012 control chromosomes in the GnomAD database, including 25,980 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 0.57 (25980 hom., cov: 31)
• Consequence: ENSG00000288921 ENST00000755294.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• Publications: 10 publications found

Genes affected

ENSG00000288921 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000288921	ENST00000755294.1	n.275+18645A>G		intron_variant	Intron 3 of 5
ENSG00000288921	ENST00000755295.1	n.350+18546A>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86371 AN: 151892 Hom.: 25931 Cov.: 31

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.569 AC: 86485 AN: 152012 Hom.: 25980 Cov.: 31 AF XY: 0.567 AC XY: 42136 AN XY: 74300

African (AFR) AF: 0.779 AC: 32316 AN: 41490

American (AMR) AF: 0.568 AC: 8668 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1785 AN: 3466

East Asian (EAS) AF: 0.627 AC: 3220 AN: 5138

South Asian (SAS) AF: 0.459 AC: 2211 AN: 4816

European-Finnish (FIN) AF: 0.444 AC: 4692 AN: 10570

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31581 AN: 67952

Other (OTH) AF: 0.587 AC: 1242 AN: 2116

Alfa AF: 0.486 Hom.: 37580

Bravo AF: 0.593

Asia WGS AF: 0.548 AC: 1905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.2
DANN	Benign	0.81
PhyloP100		-0.42

Splicing

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

Other links and lift over

dbSNP: rs4422476; hg19: chr4-118651823;