1-11908021-C-G

Variant names:

• chr1-11908021-C-G
• rs6671723
• ENST00000661075.1:n.82C>G

Variant summary

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

The ENST00000661075.1(ENSG00000285646):​n.82C>G 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 0.353 in 152,080 control chromosomes in the GnomAD database, including 9,873 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 0.35 (9873 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ENSG00000285646 ENST00000661075.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 8 publications found

Genes affected

ENSG00000285646 (HGNC:):

RNU5E-1 (HGNC:10215): (RNA, U5E small nuclear 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000661075.1. 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
	RNU5E-1	NR_002754.3		n.-131C>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285646	ENST00000661075.1		n.82C>G		non_coding_transcript_exon	Exon 1 of 2
	RNU5E-1	ENST00000362477.2	TSL:6	n.-131C>G		upstream_gene	N/A
	ENSG00000285646	ENST00000649268.2		n.-126C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53563 AN: 151960 Hom.: 9857 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.353 AC: 53618 AN: 152078 Hom.: 9873 Cov.: 33 AF XY: 0.360 AC XY: 26736 AN XY: 74340

African (AFR) AF: 0.340 AC: 14092 AN: 41470

American (AMR) AF: 0.336 AC: 5136 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 765 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2381 AN: 5176

South Asian (SAS) AF: 0.428 AC: 2062 AN: 4822

European-Finnish (FIN) AF: 0.496 AC: 5233 AN: 10558

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22979 AN: 67982

Other (OTH) AF: 0.347 AC: 732 AN: 2110

Alfa AF: 0.238 Hom.: 667

Bravo AF: 0.337

Asia WGS AF: 0.444 AC: 1543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	3.2
DANN	Benign	0.50
PhyloP100		0.52

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.

Other links and lift over

dbSNP: rs6671723;

hg19: chr1-11968078;