dbSNP rs2516740: NTHL1:c.115+600T>G (chr16-2047109-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03

Publications

10 publications found

Variant links:

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

NTHL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
NTHL1	NM_002528.7 link	c.115+600T>G	intron_variant	Intron 1 of 5	ENST00000651570.2	NP_002519.2	P78549-2E5KTI5
NTHL1	NM_001318193.2 link	c.115+600T>G	intron_variant	Intron 1 of 4		NP_001305122.2	P78549
NTHL1	NM_001318194.2 link	c.-64+600T>G	intron_variant	Intron 1 of 5		NP_001305123.1	P78549
NTHL1	XM_047434171.1 link	c.-190+600T>G	intron_variant	Intron 1 of 5		XP_047290127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTHL1	ENST00000651570.2 link	c.115+600T>G		intron_variant	Intron 1 of 5		NM_002528.7	ENSP00000498421.1		P78549-2

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46316

AN:

151984

Hom.:

8873

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.147

AC XY:

AN XY:

578

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.0758

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0942

AC:

AN:

138

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.181

AC:

132

AN:

730

Other (OTH)

AF:

0.133

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.305

AC:

46397

AN:

152102

Hom.:

8905

Cov.:

AF XY:

0.301

AC XY:

22381

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.542

AC:

22468

AN:

41456

American (AMR)

AF:

0.241

AC:

3682

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

978

AN:

3470

East Asian (EAS)

AF:

0.0226

AC:

117

AN:

5174

South Asian (SAS)

AF:

0.125

AC:

604

AN:

4832

European-Finnish (FIN)

AF:

0.243

AC:

2577

AN:

10588

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15039

AN:

67978

Other (OTH)

AF:

0.291

AC:

615

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1520

3039

4559

6078

7598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.243

Hom.:

2372

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

(source)

DANN

Benign

0.43

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over