Genetic Variant UNK:c.1105-9T>C (chr17-75817317-T-C) – 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 NM_001080419.3(UNK):c.1105-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 1,562,042 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 88 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 102 hom. )

Consequence

UNK
NM_001080419.3 intron

Scores

Splicing: ADA: 0.0001240

Clinical Significance

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

Conservation

PhyloP100: 0.365

Publications

1 publications found

Variant links:

Genes affected

UNK (HGNC:29369): (unk zinc finger) Enables mRNA CDS binding activity. Involved in cell morphogenesis involved in neuron differentiation and negative regulation of cytoplasmic translation. Part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

UNK links:

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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=-0.56).

BP6

Variant 17-75817317-T-C is Benign according to our data. Variant chr17-75817317-T-C is described in ClinVar as Benign. ClinVar VariationId is 775334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080419.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNK	NM_001080419.3	MANE Select	c.1105-9T>C		intron	N/A	NP_001073888.2	Q9C0B0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UNK	ENST00000589666.6	TSL:1 MANE Select	c.1105-9T>C	intron	N/A	ENSP00000464893.1	Q9C0B0
UNK	ENST00000925670.1		c.1222-9T>C	intron	N/A	ENSP00000595729.1
UNK	ENST00000925669.1		c.1105-9T>C	intron	N/A	ENSP00000595728.1

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2866

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0646

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00863

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.00547

AC:

1199

AN:

219098

AF XY:

0.00441

show subpopulations

Gnomad AFR exome

AF:

0.0696

Gnomad AMR exome

AF:

0.00363

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.00389

GnomAD4 exome

AF:

0.00204

AC:

2877

AN:

1409768

Hom.:

102

Cov.:

AF XY:

0.00182

AC XY:

1262

AN XY:

695282

show subpopulations

African (AFR)

AF:

0.0722

AC:

2303

AN:

31888

American (AMR)

AF:

0.00430

AC:

166

AN:

38610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23538

East Asian (EAS)

AF:

0.00

AC:

AN:

38882

South Asian (SAS)

AF:

0.000321

AC:

AN:

80912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50944

Middle Eastern (MID)

AF:

0.00374

AC:

AN:

4010

European-Non Finnish (NFE)

AF:

0.0000748

AC:

AN:

1083166

Other (OTH)

AF:

0.00495

AC:

286

AN:

57818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

133

266

398

531

664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.0189

AC:

2877

AN:

152274

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

1395

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0647

AC:

2689

AN:

41538

American (AMR)

AF:

0.00862

AC:

132

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68020

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

139

278

417

556

695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0119

Hom.:

Bravo

AF:

0.0221

Asia WGS

AF:

0.00751

AC:

AN:

3478

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

-0.56

CADD

Benign

(source)

DANN

Benign

0.57

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0040

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

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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