XR_007059816.1:n.657G>A

Variant names:

• chr6-151627231-G-A
• rs2046210
• XR_007059816.1:n.657G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The XR_007059816.1(LOC124901435):​n.657G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,962 control chromosomes in the GnomAD database, including 14,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (14125 hom., cov: 32)
• Consequence: LOC124901435 XR_007059816.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1
• Conservation: PhyloP100: -0.156
• Publications: 234 publications found

Genes affected

LOC124901435 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-151627231-G-A is Benign according to our data. Variant chr6-151627231-G-A is described in ClinVar as Benign. ClinVar VariationId is 155877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61735 AN: 151844 Hom.: 14105 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.407 AC: 61788 AN: 151962 Hom.: 14125 Cov.: 32 AF XY: 0.399 AC XY: 29605 AN XY: 74278

African (AFR) AF: 0.621 AC: 25735 AN: 41438

American (AMR) AF: 0.302 AC: 4613 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1219 AN: 3466

East Asian (EAS) AF: 0.348 AC: 1793 AN: 5152

South Asian (SAS) AF: 0.357 AC: 1719 AN: 4814

European-Finnish (FIN) AF: 0.195 AC: 2060 AN: 10552

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.344 AC: 23366 AN: 67954

Other (OTH) AF: 0.419 AC: 883 AN: 2108

Alfa AF: 0.366 Hom.: 38955

Bravo AF: 0.424

Asia WGS AF: 0.380 AC: 1322 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Estrogen resistance syndrome Pathogenic:1

Mar 01, 2014

Department of Breast and Endocrine Surgery, Kumamoto University

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

not specified Benign:1

Oct 28, 2020

H3Africa Consortium

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.729, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.39
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs2046210; hg19: chr6-151948366; COSMIC: COSV53317094;