Genetic Variant CIMAP1B:n.1303G>A (chr22-50530129-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000893016.1(TYMP):c.-248G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 373,196 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 167 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 38 hom. )

Consequence

TYMP
ENST00000893016.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.33

Publications

0 publications found

Variant links:

Genes affected

CIMAP1B (HGNC:34388): (ciliary microtubule associated protein 1B) Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CIMAP1B links:

TYMP (HGNC:3148): (thymidine phosphorylase) This gene encodes an angiogenic factor which promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells. It has a highly restricted target cell specificity acting only on endothelial cells. Mutations in this gene have been associated with mitochondrial neurogastrointestinal encephalomyopathy. Multiple alternatively spliced transcript variants have been identified. [provided by RefSeq, Apr 2012]

TYMP Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
mitochondrial DNA depletion syndrome 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
mitochondrial neurogastrointestinal encephalomyopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TYMP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 22-50530129-C-T is Benign according to our data. Variant chr22-50530129-C-T is described in ClinVar as Benign. ClinVar VariationId is 1225979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0908 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000893016.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TYMP	NM_001953.5	MANE Select	c.-236G>A	upstream_gene	N/A	NP_001944.1	E5KRG5
TYMP	NM_001257989.1		c.-236G>A	upstream_gene	N/A	NP_001244918.1	P19971-2
TYMP	NM_001113755.3		c.-248G>A	upstream_gene	N/A	NP_001107227.1	E5KRG5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CIMAP1B	ENST00000468249.1	TSL:1	n.1303G>A	non_coding_transcript_exon	Exon 4 of 4
TYMP	ENST00000893016.1		c.-248G>A	5_prime_UTR	Exon 1 of 10	ENSP00000563075.1
TYMP	ENST00000893015.1		c.-236G>A	5_prime_UTR	Exon 1 of 10	ENSP00000563074.1

Frequencies

GnomAD3 genomes

AF:

0.0278

AC:

4225

AN:

152012

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0934

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.000677

Gnomad OTH

AF:

0.0201

GnomAD4 exome

AF:

0.00468

AC:

1034

AN:

221076

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

481

AN XY:

112540

show subpopulations

African (AFR)

AF:

0.0974

AC:

604

AN:

6202

American (AMR)

AF:

0.0121

AC:

AN:

6380

Ashkenazi Jewish (ASJ)

AF:

0.00864

AC:

AN:

8102

East Asian (EAS)

AF:

0.00

AC:

AN:

20448

South Asian (SAS)

AF:

0.00

AC:

AN:

3150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19482

Middle Eastern (MID)

AF:

0.00779

AC:

AN:

1156

European-Non Finnish (NFE)

AF:

0.000755

AC:

107

AN:

141666

Other (OTH)

AF:

0.0115

AC:

167

AN:

14490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

148

198

247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0278

AC:

4228

AN:

152120

Hom.:

167

Cov.:

AF XY:

0.0274

AC XY:

2039

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0932

AC:

3870

AN:

41518

American (AMR)

AF:

0.0156

AC:

238

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000677

AC:

AN:

67952

Other (OTH)

AF:

0.0199

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

206

413

619

826

1032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0233

Hom.:

Bravo

AF:

0.0314

Asia WGS

AF:

0.00640

AC:

AN:

3452

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.81

(source)

DANN

Benign

0.84

PhyloP100

-1.3

PromoterAI

0.25

Neutral

(source)

Splicing

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