rs2516739

Variant names:

• chr16-2047157-G-A
• rs2516739
• NM_002528.7:c.115+552C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-2047157-G-A
• chr16-2047157-G-C
• chr16-2047157-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 34 publications found

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]

NTHL1 Gene-Disease associations (from GenCC):

• familial adenomatous polyposis 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, Ambry Genetics
• NTHL1-deficiency tumor predisposition syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• breast cancer

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• meningioma

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002528.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTHL1	NM_002528.7	MANE Select	c.115+552C>T		intron	N/A	NP_002519.2
	NTHL1	NM_001318193.2		c.115+552C>T		intron	N/A	NP_001305122.2
	NTHL1	NM_001318194.2		c.-64+552C>T		intron	N/A	NP_001305123.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTHL1	ENST00000651570.2	MANE Select	c.115+552C>T		intron	N/A	ENSP00000498421.1
	NTHL1	ENST00000219066.5	TSL:1	c.139+552C>T		intron	N/A	ENSP00000219066.1
	NTHL1	ENST00000623977.1	TSL:6	n.691C>T		non_coding_transcript_exon	Exon 1 of 1

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

African (AFR) AF: 0.458 AC: 11 AN: 24

American (AMR) AF: 0.112 AC: 23 AN: 206

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 7 AN: 42

East Asian (EAS) AF: 0.0294 AC: 1 AN: 34

South Asian (SAS) AF: 0.131 AC: 78 AN: 594

European-Finnish (FIN) AF: 0.194 AC: 21 AN: 108

Middle Eastern (MID) AF: 0.167 AC: 3 AN: 18

European-Non Finnish (NFE) AF: 0.193 AC: 397 AN: 2060

Other (OTH) AF: 0.146 AC: 19 AN: 130

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

African (AFR) AF: 0.515 AC: 21336 AN: 41464

American (AMR) AF: 0.235 AC: 3601 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3470

East Asian (EAS) AF: 0.0222 AC: 115 AN: 5182

South Asian (SAS) AF: 0.124 AC: 599 AN: 4830

European-Finnish (FIN) AF: 0.241 AC: 2547 AN: 10582

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14779 AN: 67984

Other (OTH) AF: 0.283 AC: 598 AN: 2110

Alfa AF: 0.241 Hom.: 18752

Bravo AF: 0.305

Asia WGS AF: 0.104 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.49
PhyloP100		-0.71
Mutation Taster		=100/0	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: rs2516739; hg19: chr16-2097158;