rs146498035

Variant names:

• chr15-75347788-G-A
• rs146498035
• ENST00000569035.5:c.-261G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-75347788-G-A
• chr15-75347788-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001256552.1(NEIL1):​c.-3G>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 0.0195 in 1,125,662 control chromosomes in the GnomAD database, including 243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (26 hom., cov: 33)
  • Exomes 𝑓: 0.020 (217 hom.)
• Consequence: NEIL1 NM_001256552.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.08
• Publications: 3 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=-0.87).
• BP6: Variant 15-75347788-G-A is Benign according to our data. Variant chr15-75347788-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1316934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0147 (2242/152234) while in subpopulation NFE AF = 0.0238 (1615/67994). AF 95% confidence interval is 0.0228. There are 26 homozygotes in GnomAd4. There are 982 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256552.1. 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+315G>A		intron	N/A	NP_078884.2	Q96FI4
	NEIL1	NM_001256552.1		c.-3G>A		5_prime_UTR	Exon 1 of 10	NP_001243481.1	Q96FI4
	NEIL1	NM_001352520.2		c.-23+315G>A		intron	N/A	NP_001339449.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL1	ENST00000569035.5	TSL:1	c.-261G>A		5_prime_UTR	Exon 1 of 10	ENSP00000455730.1	Q96FI4
	NEIL1	ENST00000355059.9	TSL:2 MANE Select	c.-23+315G>A		intron	N/A	ENSP00000347170.4	Q96FI4
	NEIL1	ENST00000564784.5	TSL:2	c.-460G>A		5_prime_UTR	Exon 1 of 11	ENSP00000457352.1	Q96FI4

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2241 AN: 152116 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.00425

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00829

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.0126 AC: 582 AN: 46176 AF XY: 0.0114

Gnomad AFR exome AF: 0.00268

Gnomad AMR exome AF: 0.00891

Gnomad ASJ exome AF: 0.0266

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00916

Gnomad NFE exome AF: 0.0214

Gnomad OTH exome AF: 0.0171

GnomAD4 exome AF: 0.0202 AC: 19657 AN: 973428 Hom.: 217 Cov.: 27 AF XY: 0.0197 AC XY: 9179 AN XY: 465342

African (AFR) AF: 0.00225 AC: 43 AN: 19126

American (AMR) AF: 0.00805 AC: 88 AN: 10926

Ashkenazi Jewish (ASJ) AF: 0.0275 AC: 229 AN: 8318

East Asian (EAS) AF: 0.00 AC: 0 AN: 7840

South Asian (SAS) AF: 0.00166 AC: 90 AN: 54316

European-Finnish (FIN) AF: 0.00809 AC: 60 AN: 7414

Middle Eastern (MID) AF: 0.0113 AC: 37 AN: 3278

European-Non Finnish (NFE) AF: 0.0223 AC: 18452 AN: 828842

Other (OTH) AF: 0.0197 AC: 658 AN: 33368

GnomAD4 genome AF: 0.0147 AC: 2242 AN: 152234 Hom.: 26 Cov.: 33 AF XY: 0.0132 AC XY: 982 AN XY: 74440

African (AFR) AF: 0.00424 AC: 176 AN: 41544

American (AMR) AF: 0.0122 AC: 186 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 113 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4828

European-Finnish (FIN) AF: 0.00829 AC: 88 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0238 AC: 1615 AN: 67994

Other (OTH) AF: 0.0147 AC: 31 AN: 2110

Alfa AF: 0.00970 Hom.: 24

Bravo AF: 0.0144

Asia WGS AF: 0.00231 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.87
CADD	Benign	1.9
DANN	Benign	0.91
PhyloP100		-1.1
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs146498035; hg19: chr15-75640129;