dbSNP rs144640614: DCLRE1B:p.Thr93Thr (chr1-113907085-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_022836.4(DCLRE1B):c.279C>T(p.Thr93Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000681 in 1,614,022 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00071 ( 1 hom. )

Consequence

DCLRE1B
NM_022836.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.409

Publications

4 publications found

Variant links:

Genes affected

DCLRE1B (HGNC:17641): (DNA cross-link repair 1B) DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1B is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000 [PubMed 10848582]).[supplied by OMIM, Mar 2008]

DCLRE1B Gene-Disease associations (from GenCC):

dyskeratosis congenita, autosomal recessive 8
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

DCLRE1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 1-113907085-C-T is Benign according to our data. Variant chr1-113907085-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 465150.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.409 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022836.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCLRE1B	NM_022836.4	MANE Select	c.279C>T	p.Thr93Thr	synonymous	Exon 2 of 4	NP_073747.1	Q9H816
DCLRE1B	NM_001363690.2		c.279C>T	p.Thr93Thr	synonymous	Exon 2 of 5	NP_001350619.1
DCLRE1B	NM_001319946.2		c.-23-924C>T		intron	N/A	NP_001306875.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCLRE1B	ENST00000650450.2	MANE Select	c.279C>T	p.Thr93Thr	synonymous	Exon 2 of 4	ENSP00000498042.1	Q9H816
DCLRE1B	ENST00000466480.2	TSL:1	n.190-924C>T		intron	N/A	ENSP00000497696.1	A0A3B3IT16
DCLRE1B	ENST00000970516.1		c.279C>T	p.Thr93Thr	synonymous	Exon 3 of 5	ENSP00000640575.1

Frequencies

GnomAD3 genomes

AF:

0.000441

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000501

AC:

126

AN:

251488

AF XY:

0.000515

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000703

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000706

AC:

1032

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000689

AC XY:

501

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.000805

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000568

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000187

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000807

AC:

897

AN:

1112002

Other (OTH)

AF:

0.000530

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

121

182

242

303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<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:

0.000440

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41466

American (AMR)

AF:

0.00137

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00104

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000625

Hom.:

Bravo

AF:

0.000578

EpiCase

AF:

0.000818

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

DCLRE1B-related disorder (1)

Hoyeraal-Hreidarsson syndrome;C3502105:Autosomal recessive dyskeratosis congenita (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.9

(source)

DANN

Benign

0.80

PhyloP100

-0.41

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over