15-75348082-C-T

Variant names:

• chr15-75348082-C-T
• rs79244935
• NM_024608.4:c.-23+609C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024608.4(NEIL1):​c.-23+609C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,006,760 control chromosomes in the GnomAD database, including 31,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3572 hom., cov: 33)
  • Exomes 𝑓: 0.25 (28218 hom.)
• Consequence: NEIL1 NM_024608.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.94
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-75348082-C-T is Benign according to our data. Variant chr15-75348082-C-T is described in ClinVar as Benign. ClinVar VariationId is 1280215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024608.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL1	NM_024608.4	MANE Select	c.-23+609C>T		intron	N/A	NP_078884.2	Q96FI4
	NEIL1	NM_001256552.1		c.236+56C>T		intron	N/A	NP_001243481.1	Q96FI4
	NEIL1	NM_001352520.2		c.-23+609C>T		intron	N/A	NP_001339449.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL1	ENST00000355059.9	TSL:2 MANE Select	c.-23+609C>T		intron	N/A	ENSP00000347170.4	Q96FI4
	NEIL1	ENST00000569035.5	TSL:1	c.-23+56C>T		intron	N/A	ENSP00000455730.1	Q96FI4
	NEIL1	ENST00000866915.1		c.-23+609C>T		intron	N/A	ENSP00000536974.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30946 AN: 152030 Hom.: 3569 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.251 AC: 214351 AN: 854612 Hom.: 28218 Cov.: 12 AF XY: 0.247 AC XY: 100365 AN XY: 406914

African (AFR) AF: 0.160 AC: 2568 AN: 16076

American (AMR) AF: 0.0934 AC: 630 AN: 6746

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 925 AN: 6432

East Asian (EAS) AF: 0.0244 AC: 133 AN: 5444

South Asian (SAS) AF: 0.0681 AC: 2818 AN: 41404

European-Finnish (FIN) AF: 0.274 AC: 1350 AN: 4924

Middle Eastern (MID) AF: 0.0848 AC: 148 AN: 1746

European-Non Finnish (NFE) AF: 0.269 AC: 199728 AN: 743310

Other (OTH) AF: 0.212 AC: 6051 AN: 28530

GnomAD4 genome AF: 0.203 AC: 30950 AN: 152148 Hom.: 3572 Cov.: 33 AF XY: 0.201 AC XY: 14922 AN XY: 74402

African (AFR) AF: 0.162 AC: 6738 AN: 41534

American (AMR) AF: 0.130 AC: 1994 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 539 AN: 3468

East Asian (EAS) AF: 0.0227 AC: 117 AN: 5144

South Asian (SAS) AF: 0.0611 AC: 295 AN: 4828

European-Finnish (FIN) AF: 0.296 AC: 3137 AN: 10604

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.257 AC: 17466 AN: 67954

Other (OTH) AF: 0.178 AC: 377 AN: 2114

Alfa AF: 0.239 Hom.: 605

Bravo AF: 0.191

Asia WGS AF: 0.0490 AC: 172 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.72
PhyloP100		-5.9
PromoterAI		0.00080	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs79244935; hg19: chr15-75640423;