15-75351274-CTTTTTTTTT-CTTTTTT

Variant names:

• chr15-75351274-CTTT-C
• rs11422837
• NM_024608.4:c.435-820_435-818delTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001352519.2(NEIL1):​c.100-10_100-8delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 347,752 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 0.00020 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0081 (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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00813 (1843/226628) while in subpopulation AFR AF= 0.0198 (104/5250). AF 95% confidence interval is 0.0167. There are 0 homozygotes in gnomad4_exome. There are 984 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL1	NM_024608.4	c.435-820_435-818delTTT		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_435-834delTTT		intron_variant	Intron 2 of 9	2	NM_024608.4	ENSP00000347170.4

Frequencies

GnomAD3 genomes AF: 0.000198 AC: 24 AN: 121124 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: 0.000553

Gnomad FIN AF: 0.000243

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000355

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00813 AC: 1843 AN: 226628 Hom.: 0 AF XY: 0.00755 AC XY: 984 AN XY: 130412

Gnomad4 AFR exome AF: 0.0198

Gnomad4 AMR exome AF: 0.0119

Gnomad4 ASJ exome AF: 0.00926

Gnomad4 EAS exome AF: 0.0130

Gnomad4 SAS exome AF: 0.00546

Gnomad4 FIN exome AF: 0.00707

Gnomad4 NFE exome AF: 0.00786

Gnomad4 OTH exome AF: 0.00777

GnomAD4 genome AF: 0.000198 AC: 24 AN: 121124 Hom.: 0 Cov.: 0 AF XY: 0.000142 AC XY: 8 AN XY: 56364

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000553

Gnomad4 FIN AF: 0.000243

Gnomad4 NFE AF: 0.000355

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)		0.020		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;