15-75351274-CTTTTTTTTT-CTTTTTTT

Variant names:

• chr15-75351274-CTT-C
• rs11422837
• NM_024608.4:c.435-819_435-818delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001352519.2(NEIL1):​c.100-9_100-8delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 328,410 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 0.00036 (0 hom., cov: 0)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: NEIL1 NM_001352519.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL1	NM_024608.4	c.435-819_435-818delTT		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_435-835delTT		intron_variant	Intron 2 of 9	2	NM_024608.4	ENSP00000347170.4

Frequencies

GnomAD3 genomes AF: 0.000355 AC: 43 AN: 121100 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000692

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000729

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0421 AC: 8732 AN: 207316 Hom.: 0 AF XY: 0.0396 AC XY: 4706 AN XY: 118876

Gnomad4 AFR exome AF: 0.0739

Gnomad4 AMR exome AF: 0.0503

Gnomad4 ASJ exome AF: 0.0454

Gnomad4 EAS exome AF: 0.0432

Gnomad4 SAS exome AF: 0.0348

Gnomad4 FIN exome AF: 0.0388

Gnomad4 NFE exome AF: 0.0419

Gnomad4 OTH exome AF: 0.0465

GnomAD4 genome AF: 0.000355 AC: 43 AN: 121094 Hom.: 0 Cov.: 0 AF XY: 0.000390 AC XY: 22 AN XY: 56358

Gnomad4 AFR AF: 0.000691

Gnomad4 AMR AF: 0.000268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000729

Gnomad4 NFE AF: 0.000236

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;