rs2516740

chr16-2047109-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002528.7(NTHL1):c.115+600T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 153,120 control chromosomes in the GnomAD database, including 8,920 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (8905 hom., cov: 33)
  • Exomes 𝑓: 0.16 (15 hom.)
• Consequence: NTHL1 NM_002528.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

NTHL1 (HGNC:8028): (nth like DNA glycosylase 1) The protein encoded by this gene is a DNA N-glycosylase of the endonuclease III family. Like a similar protein in E. coli, the encoded protein has DNA glycosylase activity on DNA substrates containing oxidized pyrimidine residues and has apurinic/apyrimidinic lyase activity. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTHL1	NM_002528.7	c.115+600T>G		intron_variant		ENST00000651570.2
NTHL1	NM_001318193.2	c.115+600T>G		intron_variant
NTHL1	NM_001318194.2	c.-64+600T>G		intron_variant
NTHL1	XM_047434171.1	c.-190+600T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTHL1	ENST00000651570.2	c.115+600T>G		intron_variant			NM_002528.7

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46316 AN: 151984 Hom.: 8873 Cov.: 33

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.0224

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.159 AC: 162 AN: 1018 Hom.: 15 Cov.: 0 AF XY: 0.147 AC XY: 85 AN XY: 578

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.0758

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0942

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.305 AC: 46397 AN: 152102 Hom.: 8905 Cov.: 33 AF XY: 0.301 AC XY: 22381 AN XY: 74346

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.291

Alfa AF: 0.256 Hom.: 1614

Bravo AF: 0.317

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.7
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2516740; hg19: chr16-2097110;