15-75351274-CTTTTTTTTT-CT

Variant names:

• chr15-75351274-CTTTTTTTT-C
• rs11422837
• NM_024608.4:c.435-825_435-818delTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001352519.2(NEIL1):​c.100-15_100-8delTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000083 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000083 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEIL1 NM_001352519.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 0 publications found

Genes affected

NEIL1 (HGNC:18448): (nei like DNA glycosylase 1) This gene is a member of the Nei endonuclease VIII-like gene family which encodes DNA glycosylases. The encoded enzyme participates in the DNA repair pathway by initiating base excision repair by removing damaged bases, primarily oxidized pyrimidines. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352519.2. 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
	NEIL1	NM_024608.4	MANE Select	c.435-825_435-818delTTTTTTTT		intron	N/A	NP_078884.2	Q96FI4
	NEIL1	NM_001256552.1		c.693-825_693-818delTTTTTTTT		intron	N/A	NP_001243481.1	Q96FI4
	NEIL1	NM_001352520.2		c.129-825_129-818delTTTTTTTT		intron	N/A	NP_001339449.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL1	ENST00000355059.9	TSL:2 MANE Select	c.435-836_435-829delTTTTTTTT		intron	N/A	ENSP00000347170.4	Q96FI4
	NEIL1	ENST00000569035.5	TSL:1	c.435-836_435-829delTTTTTTTT		intron	N/A	ENSP00000455730.1	Q96FI4
	NEIL1	ENST00000866915.1		c.435-836_435-829delTTTTTTTT		intron	N/A	ENSP00000536974.1

Frequencies

GnomAD3 genomes AF: 0.00000825 AC: 1 AN: 121146 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000169

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000831 AC: 2 AN: 240572 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 138462

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

African (AFR) AF: 0.00 AC: 0 AN: 5582

American (AMR) AF: 0.00 AC: 0 AN: 16540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7802

East Asian (EAS) AF: 0.00 AC: 0 AN: 8230

South Asian (SAS) AF: 0.00 AC: 0 AN: 46392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 846

European-Non Finnish (NFE) AF: 0.0000149 AC: 2 AN: 134372

Other (OTH) AF: 0.00 AC: 0 AN: 11222

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000812204), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000825 AC: 1 AN: 121146 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 56372

African (AFR) AF: 0.00 AC: 0 AN: 33262

American (AMR) AF: 0.00 AC: 0 AN: 11188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3114

East Asian (EAS) AF: 0.00 AC: 0 AN: 3918

South Asian (SAS) AF: 0.00 AC: 0 AN: 3614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 246

European-Non Finnish (NFE) AF: 0.0000169 AC: 1 AN: 59240

Other (OTH) AF: 0.00 AC: 0 AN: 1622

Alfa AF: 0.00 Hom.: 282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs11422837; hg19: chr15-75643615;