rs4876377

Variant names:

• chr8-117474750-C-T
• rs4876377
• ENST00000751876.1:n.273-2422G>A

Variant summary

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

The ENST00000751876.1(ENSG00000297933):​n.273-2422G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,140 control chromosomes in the GnomAD database, including 4,411 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 0.21 (4411 hom., cov: 32)
• Consequence: ENSG00000297933 ENST00000751876.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 1 publications found

Genes affected

ENSG00000297933 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375716	XR_007061067.1	n.307-33538G>A		intron_variant	Intron 2 of 5
LOC105375716	XR_007061068.1	n.307-8843G>A		intron_variant	Intron 2 of 7
LOC105375716	XR_928568.4	n.224-8843G>A		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000297933	ENST00000751876.1	n.273-2422G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32562 AN: 152022 Hom.: 4413 Cov.: 32

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.0649

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.214 AC: 32561 AN: 152140 Hom.: 4411 Cov.: 32 AF XY: 0.210 AC XY: 15628 AN XY: 74366

African (AFR) AF: 0.0661 AC: 2747 AN: 41560

American (AMR) AF: 0.203 AC: 3105 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1208 AN: 3468

East Asian (EAS) AF: 0.0651 AC: 337 AN: 5178

South Asian (SAS) AF: 0.262 AC: 1265 AN: 4826

European-Finnish (FIN) AF: 0.218 AC: 2307 AN: 10562

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20662 AN: 67956

Other (OTH) AF: 0.229 AC: 484 AN: 2112

Alfa AF: 0.250 Hom.: 662

Bravo AF: 0.204

Asia WGS AF: 0.170 AC: 593 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.35
PhyloP100		0.064

Splicing

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

Other links and lift over

dbSNP: rs4876377; hg19: chr8-118486989;