15-75348228-A-G

Position:

• chr15-75348228-A-G

Variant summary

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

The NM_024608.4(NEIL1):​c.-22-656A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 801,326 control chromosomes in the GnomAD database, including 89,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15420 hom., cov: 33)
  • Exomes 𝑓: 0.48 (74393 hom.)
• Consequence: NEIL1 NM_024608.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.87

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-75348228-A-G is Benign according to our data. Variant chr15-75348228-A-G is described in ClinVar as [Benign]. Clinvar id is 1236664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEIL1	NM_024608.4	c.-22-656A>G		intron_variant		ENST00000355059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEIL1	ENST00000355059.9	c.-22-656A>G		intron_variant		2	NM_024608.4	P1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66719 AN: 151742 Hom.: 15424 Cov.: 33

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.475 AC: 308577 AN: 649474 Hom.: 74393 Cov.: 8 AF XY: 0.475 AC XY: 143831 AN XY: 302496

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.610

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.534

Gnomad4 SAS exome AF: 0.541

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.478

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.439 AC: 66731 AN: 151852 Hom.: 15420 Cov.: 33 AF XY: 0.441 AC XY: 32745 AN XY: 74220

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.440

Alfa AF: 0.452 Hom.: 2005

Bravo AF: 0.439

Asia WGS AF: 0.517 AC: 1793 AN: 3466

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.24

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: rs8030014; hg19: chr15-75640569;