chr4-177339718-C-T

Variant names:

• chr4-177339718-C-T
• rs12645561
• NM_018248.3:c.628-65C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018248.3(NEIL3):​c.628-65C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,016,098 control chromosomes in the GnomAD database, including 9,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1036 hom., cov: 32)
  • Exomes 𝑓: 0.13 (8878 hom.)
• Consequence: NEIL3 NM_018248.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.697
• Publications: 15 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-177339718-C-T is Benign according to our data. Variant chr4-177339718-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018248.3. 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.628-65C>T		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.628-65C>T		intron	N/A	ENSP00000264596.3	Q8TAT5
	NEIL3	ENST00000513321.1	TSL:1	n.*313+3397C>T		intron	N/A	ENSP00000424735.1	D6RAV1
	NEIL3	ENST00000905043.1		c.628-65C>T		intron	N/A	ENSP00000575102.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15821 AN: 151994 Hom.: 1036 Cov.: 32

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0920

GnomAD4 exome AF: 0.135 AC: 116541 AN: 863986 Hom.: 8878 AF XY: 0.135 AC XY: 60903 AN XY: 452252

African (AFR) AF: 0.0327 AC: 692 AN: 21144

American (AMR) AF: 0.147 AC: 5652 AN: 38492

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 1423 AN: 21362

East Asian (EAS) AF: 0.319 AC: 11635 AN: 36478

South Asian (SAS) AF: 0.154 AC: 10812 AN: 69990

European-Finnish (FIN) AF: 0.129 AC: 6599 AN: 51162

Middle Eastern (MID) AF: 0.0632 AC: 286 AN: 4526

European-Non Finnish (NFE) AF: 0.128 AC: 74378 AN: 580498

Other (OTH) AF: 0.126 AC: 5064 AN: 40334

GnomAD4 genome AF: 0.104 AC: 15828 AN: 152112 Hom.: 1036 Cov.: 32 AF XY: 0.105 AC XY: 7842 AN XY: 74346

African (AFR) AF: 0.0374 AC: 1551 AN: 41510

American (AMR) AF: 0.112 AC: 1714 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3470

East Asian (EAS) AF: 0.302 AC: 1562 AN: 5174

South Asian (SAS) AF: 0.164 AC: 791 AN: 4814

European-Finnish (FIN) AF: 0.136 AC: 1433 AN: 10558

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8297 AN: 68008

Other (OTH) AF: 0.0920 AC: 194 AN: 2108

Alfa AF: 0.111 Hom.: 1693

Bravo AF: 0.103

Asia WGS AF: 0.222 AC: 772 AN: 3478

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
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.71
PhyloP100		-0.70
Mutation Taster		=19/81	disease causing (long InDel)

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: rs12645561; hg19: chr4-178260872; COSMIC: COSV52808872; COSMIC: COSV52808872;