rs4656784

Variant names:

• chr1-159357090-A-G
• rs4656784
• ENST00000431862.1:n.539+4684T>C

Variant summary

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

The ENST00000431862.1(ENSG00000228560):​n.539+4684T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,868 control chromosomes in the GnomAD database, including 2,022 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 0.14 (2022 hom., cov: 32)
• Consequence: ENSG00000228560 ENST00000431862.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 15 publications found

Genes affected

ENSG00000228560 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124904433	XR_007066672.1	n.186+7234T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000228560	ENST00000431862.1	n.539+4684T>C		intron_variant	Intron 3 of 3	1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21499 AN: 151750 Hom.: 2022 Cov.: 32

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.142 AC: 21494 AN: 151868 Hom.: 2022 Cov.: 32 AF XY: 0.140 AC XY: 10387 AN XY: 74224

African (AFR) AF: 0.0368 AC: 1529 AN: 41526

American (AMR) AF: 0.131 AC: 2005 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5188

South Asian (SAS) AF: 0.118 AC: 571 AN: 4824

European-Finnish (FIN) AF: 0.205 AC: 2167 AN: 10554

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14391 AN: 67750

Other (OTH) AF: 0.158 AC: 332 AN: 2102

Alfa AF: 0.187 Hom.: 4568

Bravo AF: 0.131

Asia WGS AF: 0.0440 AC: 153 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.53
PhyloP100		0.32

Splicing

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

Other links and lift over

dbSNP: rs4656784; hg19: chr1-159326880;