rs754523

Variant names:

• chr2-21088819-A-G
• rs754523
• ENST00000821616.1:n.239+7535T>C

Variant summary

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

The ENST00000821616.1(ENSG00000287956):​n.239+7535T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,130 control chromosomes in the GnomAD database, including 6,081 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 0.28 (6081 hom., cov: 32)
• Consequence: ENSG00000287956 ENST00000821616.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 36 publications found

Genes affected

ENSG00000287956 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124905593	XR_007088659.1	n.579-7302A>G		intron_variant	Intron 1 of 2
LOC124905593	XR_007088660.1	n.579-7302A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287956	ENST00000821616.1	n.239+7535T>C		intron_variant	Intron 1 of 1
ENSG00000287956	ENST00000821617.1	n.261+7535T>C		intron_variant	Intron 1 of 2
ENSG00000287956	ENST00000821618.1	n.241+7535T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42326 AN: 152012 Hom.: 6083 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.278 AC: 42340 AN: 152130 Hom.: 6081 Cov.: 32 AF XY: 0.276 AC XY: 20484 AN XY: 74338

African (AFR) AF: 0.218 AC: 9027 AN: 41496

American (AMR) AF: 0.321 AC: 4906 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3472

East Asian (EAS) AF: 0.268 AC: 1387 AN: 5172

South Asian (SAS) AF: 0.157 AC: 757 AN: 4824

European-Finnish (FIN) AF: 0.272 AC: 2876 AN: 10578

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.317 AC: 21579 AN: 67992

Other (OTH) AF: 0.263 AC: 555 AN: 2112

Alfa AF: 0.288 Hom.: 5081

Bravo AF: 0.283

Asia WGS AF: 0.203 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.79
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs754523; hg19: chr2-21311691;