rs2516739

chr16-2047157-G-A

Variant summary

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

The NM_002528.7(NTHL1):c.115+552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 155,340 control chromosomes in the GnomAD database, including 8,243 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 0.29 (8187 hom., cov: 33)
  • Exomes 𝑓: 0.17 (56 hom.)
• Consequence: NTHL1 NM_002528.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTHL1	NM_002528.7	c.115+552C>T		intron_variant		ENST00000651570.2
NTHL1	NM_001318193.2	c.115+552C>T		intron_variant
NTHL1	NM_001318194.2	c.-64+552C>T		intron_variant
NTHL1	XM_047434171.1	c.-190+552C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTHL1	ENST00000651570.2	c.115+552C>T		intron_variant			NM_002528.7

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44781 AN: 152006 Hom.: 8160 Cov.: 33

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0219

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.174 AC: 560 AN: 3216 Hom.: 56 Cov.: 0 AF XY: 0.170 AC XY: 293 AN XY: 1720

Gnomad4 AFR exome AF: 0.458

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.0294

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.295 AC: 44857 AN: 152124 Hom.: 8187 Cov.: 33 AF XY: 0.292 AC XY: 21698 AN XY: 74358

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.0222

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.283

Alfa AF: 0.233 Hom.: 6531

Bravo AF: 0.305

Asia WGS AF: 0.104 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.9
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs2516739; hg19: chr16-2097158;