dbSNP rs1024611: ENSG00000301139:n.-249T>C (chr17-34252769-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The ENST00000776537.1(ENSG00000301139):n.-249T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. Note: ENST00000776537.1 is not a MANE Select or MANE Plus Clinical transcript for ENSG00000301139; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.287 (AC=43,619) in the gnomAD database across 152,162 control chromosomes, including 6,922 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.539. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Variant has been reported in ClinVar as Uncertain Significance (★).

Frequency

Genomes: 𝑓 0.29 ( 6922 hom., cov: 33)

Consequence

ENSG00000301139
ENST00000776537.1 upstream_gene

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:2

Conservation

PhyloP100: -0.103

Publications

312 publications found

Variant links:

Genes affected

ENSG00000301139 (HGNC:):

ENSG00000301139 links:

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new If you want to explore the variant's impact on the transcript ENST00000776537.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.5392 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

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

show subpopulations

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.:

AF XY:

0.296

AC XY:

21990

AN XY:

74382

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.275

AC:

18686

AN:

68006

Other (OTH)

AF:

0.284

AC:

601

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1565

3130

4696

6261

7826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

TOPMed (Bravo)

AF:

0.290

AC:

76670

AN:

264690

Hom.:

12496

ALFA (dbGaP/dbSNP Allele Frequency Aggregator)

AF:

0.279

AC:

143748

AN:

514420

Hom.:

21089

Local populations

ABraOM SABE-WGS-1171

AF:

0.312

AC:

730

AN:

2342

Hom.:

112

ChinaMAP Phase 1

AF:

0.573

Denmark Genome

AF:

0.370

AC:

111

AN:

300

GenomeAsia100K

AF:

0.439

AC:

1527

AN:

3478

show subpopulations

Oceania

AF:

0.392

AC:

AN:

148

Hom.:

North-East Asia

AF:

0.617

AC:

433

AN:

702

Hom.:

134

South-East Asia

AF:

0.512

AC:

354

AN:

692

Hom.:

South Asia

AF:

0.364

AC:

527

AN:

1448

Hom.:

111

Africa

AF:

0.178

AC:

AN:

208

Hom.:

America

AF:

0.788

AC:

AN:

Hom.:

West Eurasia

AF:

0.338

AC:

AN:

228

Hom.:

Korea4K (4,157 Koreans)

AF:

0.616

AC:

4455

AN:

7234

Qatari Genome

AF:

0.324

AC:

AN:

176

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.663

AC:

81432

AN:

122802

Hom.:

26991

Turkish Variome

AF:

0.291

AC:

450

AN:

1546

Hom.:

UK10K

AF:

0.283

AC:

2143

AN:

7562

show subpopulations

TwinsUK

AF:

0.278

AC:

992

AN:

3574

ALSPAC

AF:

0.289

AC:

1113

AN:

3854

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.556

AC:

4981

AN:

8960

Hom.:

1377

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

CCL2-related disorder (2)

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

(source)

DANN

Benign

0.46

PhyloP100

-0.10

AlphaGenome AVI

Benign

1.2

(source)

GPN-Star LLR

0.16

(source)

GPN-Star score

-0.16

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over