15-75347736-G-A

Position:

• chr15-75347736-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001256552.1(NEIL1):​c.-55G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 945,970 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (75 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (39 hom.)
• Consequence: NEIL1 NM_001256552.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.695

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]

NEIL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-75347736-G-A is Benign according to our data. Variant chr15-75347736-G-A is described in ClinVar as [Benign]. Clinvar id is 1268945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.057 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL1	NM_024608.4	c.-23+263G>A		intron_variant		ENST00000355059.9	NP_078884.2
NEIL1	NM_001256552.1	c.-55G>A		5_prime_UTR_variant	1/10		NP_001243481.1
NEIL1	NM_001352520.2	c.-23+263G>A		intron_variant			NP_001339449.1
NEIL1	NM_001352519.2	c.-358+263G>A		intron_variant			NP_001339448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEIL1	ENST00000355059.9	c.-23+263G>A		intron_variant		2	NM_024608.4	ENSP00000347170.4

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2611 AN: 152134 Hom.: 75 Cov.: 33

Gnomad AFR AF: 0.0592

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00958

GnomAD4 exome AF: 0.00152 AC: 1206 AN: 793720 Hom.: 39 Cov.: 11 AF XY: 0.00142 AC XY: 538 AN XY: 378992

Gnomad4 AFR exome AF: 0.0629

Gnomad4 AMR exome AF: 0.00256

Gnomad4 ASJ exome AF: 0.00382

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000152

Gnomad4 OTH exome AF: 0.00311

GnomAD4 genome AF: 0.0171 AC: 2609 AN: 152250 Hom.: 75 Cov.: 33 AF XY: 0.0169 AC XY: 1259 AN XY: 74450

Gnomad4 AFR AF: 0.0590

Gnomad4 AMR AF: 0.00712

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.00948

Alfa AF: 0.0139 Hom.: 8

Bravo AF: 0.0198

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 16, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs114767302; hg19: chr15-75640077;