4-177335824-TAA-TAAA

Variant names:

• chr4-177335824-T-TA
• rs35737622
• NM_018248.3:c.413+10dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000264596.4(NEIL3):​c.413+2_413+3insA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.044 in 1,525,280 control chromosomes in the GnomAD database, including 3,038 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (309 hom., cov: 32)
  • Exomes 𝑓: 0.044 (2729 hom.)
• Consequence: NEIL3 ENST00000264596.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.03
• Publications: 5 publications found

Genes affected

NEIL3 (HGNC:24573): (nei like DNA glycosylase 3) NEIL3 belongs to a class of DNA glycosylases homologous to the bacterial Fpg/Nei family. These glycosylases initiate the first step in base excision repair by cleaving bases damaged by reactive oxygen species and introducing a DNA strand break via the associated lyase reaction (Bandaru et al., 2002 [PubMed 12509226]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 4-177335824-T-TA is Benign according to our data. Variant chr4-177335824-T-TA is described in ClinVar as Benign. ClinVar VariationId is 2688512.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000264596.4. 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
	NEIL3	NM_018248.3	MANE Select	c.413+10dupA		intron	N/A	NP_060718.3	Q8TAT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL3	ENST00000264596.4	TSL:1 MANE Select	c.413+2_413+3insA		splice_region intron	N/A	ENSP00000264596.3	Q8TAT5
	NEIL3	ENST00000513321.1	TSL:1	n.*99+2_*99+3insA		splice_region intron	N/A	ENSP00000424735.1	D6RAV1
	NEIL3	ENST00000905043.1		c.413+2_413+3insA		splice_region intron	N/A	ENSP00000575102.1

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6707 AN: 151886 Hom.: 309 Cov.: 32

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.00867

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0308

Gnomad OTH AF: 0.0500

GnomAD2 exomes AF: 0.0595 AC: 11059 AN: 185788 AF XY: 0.0554

Gnomad AFR exome AF: 0.0326

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.0120

Gnomad EAS exome AF: 0.274

Gnomad FIN exome AF: 0.0159

Gnomad NFE exome AF: 0.0324

Gnomad OTH exome AF: 0.0492

GnomAD4 exome AF: 0.0440 AC: 60469 AN: 1373278 Hom.: 2729 Cov.: 31 AF XY: 0.0435 AC XY: 29495 AN XY: 678336

African (AFR) AF: 0.0311 AC: 919 AN: 29582

American (AMR) AF: 0.109 AC: 2959 AN: 27224

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 251 AN: 22192

East Asian (EAS) AF: 0.292 AC: 10988 AN: 37682

South Asian (SAS) AF: 0.0518 AC: 3690 AN: 71246

European-Finnish (FIN) AF: 0.0165 AC: 837 AN: 50608

Middle Eastern (MID) AF: 0.0222 AC: 107 AN: 4830

European-Non Finnish (NFE) AF: 0.0353 AC: 37866 AN: 1073782

Other (OTH) AF: 0.0508 AC: 2852 AN: 56132

GnomAD4 genome AF: 0.0442 AC: 6716 AN: 152002 Hom.: 309 Cov.: 32 AF XY: 0.0447 AC XY: 3322 AN XY: 74288

African (AFR) AF: 0.0334 AC: 1386 AN: 41470

American (AMR) AF: 0.0752 AC: 1147 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00867 AC: 30 AN: 3462

East Asian (EAS) AF: 0.279 AC: 1439 AN: 5154

South Asian (SAS) AF: 0.0656 AC: 316 AN: 4818

European-Finnish (FIN) AF: 0.0175 AC: 185 AN: 10558

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0308 AC: 2095 AN: 67982

Other (OTH) AF: 0.0518 AC: 109 AN: 2104

Alfa AF: 0.0161 Hom.: 16

Bravo AF: 0.0526

Asia WGS AF: 0.160 AC: 555 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0
Mutation Taster		=95/5	polymorphism (auto)

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: rs35737622; hg19: chr4-178256978; COSMIC: COSV99220027;