15-75351274-CTTTTTTTTT-CTTTTT

Variant names:

• chr15-75351274-CTTTT-C
• rs11422837
• NM_024608.4:c.435-821_435-818delTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001352519.2(NEIL1):​c.100-11_100-8delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 357,494 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0019 (0 hom.)
• Consequence: NEIL1 NM_001352519.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL1	NM_024608.4	c.435-821_435-818delTTTT		intron_variant	Intron 2 of 9	ENST00000355059.9	NP_078884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL1	ENST00000355059.9	c.435-836_435-833delTTTT		intron_variant	Intron 2 of 9	2	NM_024608.4	ENSP00000347170.4

Frequencies

GnomAD3 genomes AF: 0.0000660 AC: 8 AN: 121124 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000902

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000277

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000675

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00187 AC: 442 AN: 236370 Hom.: 0 AF XY: 0.00171 AC XY: 233 AN XY: 136112

Gnomad4 AFR exome AF: 0.00369

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.00249

Gnomad4 EAS exome AF: 0.00617

Gnomad4 SAS exome AF: 0.00107

Gnomad4 FIN exome AF: 0.00149

Gnomad4 NFE exome AF: 0.00178

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome AF: 0.0000660 AC: 8 AN: 121124 Hom.: 0 Cov.: 0 AF XY: 0.0000710 AC XY: 4 AN XY: 56362

Gnomad4 AFR AF: 0.0000902

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000277

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000675

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11422837; hg19: chr15-75643615;