rs2996127

Variant names:

• chr6-58035886-A-G
• rs2996127
• ENST00000641775.1:n.224-7549A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000641775.1(ENSG00000225096):​n.224-7549A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 148,800 control chromosomes in the GnomAD database, including 4,892 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 0.24 (4892 hom., cov: 28)
• Consequence: ENSG00000225096 ENST00000641775.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 1 publications found

Genes affected

ENSG00000225096 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BS2: High Homozygotes in GnomAd4 at 4892 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901336	XR_007059628.1	n.31-2095T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000225096	ENST00000641775.1	n.224-7549A>G		intron_variant	Intron 2 of 5
ENSG00000225096	ENST00000641829.1	n.496-7549A>G		intron_variant	Intron 5 of 7
ENSG00000225096	ENST00000666847.1	n.177-7549A>G		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.240 AC: 35698 AN: 148686 Hom.: 4883 Cov.: 28

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.240 AC: 35735 AN: 148800 Hom.: 4892 Cov.: 28 AF XY: 0.232 AC XY: 16820 AN XY: 72622

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.378 AC: 15097 AN: 39980

American (AMR) AF: 0.173 AC: 2597 AN: 15034

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 818 AN: 3416

East Asian (EAS) AF: 0.0996 AC: 506 AN: 5078

South Asian (SAS) AF: 0.139 AC: 652 AN: 4682

European-Finnish (FIN) AF: 0.157 AC: 1631 AN: 10368

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.206 AC: 13794 AN: 66996

Other (OTH) AF: 0.220 AC: 452 AN: 2056

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.229 Hom.: 483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.52
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs2996127; hg19: chr6-58362164;