chr15-75351274-C-CTT

Position:

• chr15-75351274-C-CTT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_024608.4(NEIL1):​c.435-819_435-818dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0085 (28 hom., cov: 0)
  • Exomes 𝑓: 0.033 (4 hom.)
• Consequence: NEIL1 NM_024608.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• 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 -9 ACMG points.

• BP6: Variant 15-75351274-C-CTT is Benign according to our data. Variant chr15-75351274-C-CTT is described in ClinVar as [Benign]. Clinvar id is 3037264.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0325 (7639/235036) while in subpopulation EAS AF= 0.0429 (348/8114). AF 95% confidence interval is 0.0406. There are 4 homozygotes in gnomad4_exome. There are 4332 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEIL1	NM_024608.4	c.435-819_435-818dup		intron_variant		ENST00000355059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEIL1	ENST00000355059.9	c.435-819_435-818dup		intron_variant		2	NM_024608.4	P1

Frequencies

GnomAD3 genomes AF: 0.00852 AC: 1032 AN: 121120 Hom.: 28 Cov.: 0

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.00369

Gnomad AMR AF: 0.00840

Gnomad ASJ AF: 0.00514

Gnomad EAS AF: 0.00357

Gnomad SAS AF: 0.0138

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0123

GnomAD4 exome AF: 0.0325 AC: 7639 AN: 235036 Hom.: 4 Cov.: 0 AF XY: 0.0320 AC XY: 4332 AN XY: 135366

Gnomad4 AFR exome AF: 0.0216

Gnomad4 AMR exome AF: 0.0360

Gnomad4 ASJ exome AF: 0.0266

Gnomad4 EAS exome AF: 0.0429

Gnomad4 SAS exome AF: 0.0422

Gnomad4 FIN exome AF: 0.0276

Gnomad4 NFE exome AF: 0.0297

Gnomad4 OTH exome AF: 0.0277

GnomAD4 genome AF: 0.00851 AC: 1031 AN: 121114 Hom.: 28 Cov.: 0 AF XY: 0.00867 AC XY: 489 AN XY: 56374

Gnomad4 AFR AF: 0.00390

Gnomad4 AMR AF: 0.00840

Gnomad4 ASJ AF: 0.00514

Gnomad4 EAS AF: 0.00359

Gnomad4 SAS AF: 0.0136

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.0122

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NEIL1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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;