ENST00000776537.1:n.-249T>C

Variant names:

• chr17-34252769-A-G
• rs1024611
• ENST00000776537.1:n.-249T>C

Variant summary

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

The ENST00000776537.1(ENSG00000301139):​n.-249T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,162 control chromosomes in the GnomAD database, including 6,922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.29 (6922 hom., cov: 33)
• Consequence: ENSG00000301139 ENST00000776537.1 upstream_gene
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:2
• Conservation: PhyloP100: -0.103
• Publications: 310 publications found

Genes affected

ENSG00000301139 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000776537.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000301139	ENST00000776537.1		n.-249T>C		upstream_gene	N/A
	ENSG00000301139	ENST00000776538.1		n.-249T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43582 AN: 152044 Hom.: 6908 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.287 AC: 43619 AN: 152162 Hom.: 6922 Cov.: 33 AF XY: 0.296 AC XY: 21990 AN XY: 74382

African (AFR) AF: 0.201 AC: 8359 AN: 41512

American (AMR) AF: 0.432 AC: 6604 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 980 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2870 AN: 5160

South Asian (SAS) AF: 0.344 AC: 1660 AN: 4830

European-Finnish (FIN) AF: 0.344 AC: 3643 AN: 10586

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18686 AN: 68006

Other (OTH) AF: 0.284 AC: 601 AN: 2116

Alfa AF: 0.281 Hom.: 20326

Bravo AF: 0.290

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	1	CCL2-related disorder (2)
-	-	1	Spina bifida, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.46
PhyloP100		-0.10

Splicing

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

Other links and lift over

dbSNP: rs1024611; hg19: chr17-32579788;