dbSNP rs6053733: SHLD1:c.179-28596A>G (chr20-5834428-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_152504.4(SHLD1):c.179-28596A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,064 control chromosomes in the GnomAD database, including 9,382 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 0.34 ( 9382 hom., cov: 32)

Consequence

SHLD1
NM_152504.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0150

Publications

4 publications found

Variant links:

Genes affected

SHLD1 (HGNC:26318): (shieldin complex subunit 1) Involved in negative regulation of double-strand break repair via homologous recombination; positive regulation of double-strand break repair via nonhomologous end joining; and positive regulation of isotype switching. Located in site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

SHLD1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_152504.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152504.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SHLD1	NM_152504.4	MANE Select	c.179-28596A>G	intron	N/A	NP_689717.2
SHLD1	NM_001303477.2		c.179-28596A>G	intron	N/A	NP_001290406.1	Q8IYI0-1
SHLD1	NM_001303478.2		c.83-28596A>G	intron	N/A	NP_001290407.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SHLD1	ENST00000303142.11	TSL:1 MANE Select	c.179-28596A>G	intron	N/A	ENSP00000305875.6	Q8IYI0-1
SHLD1	ENST00000875759.1		c.179-28596A>G	intron	N/A	ENSP00000545818.1
SHLD1	ENST00000915775.1		c.179-28596A>G	intron	N/A	ENSP00000585834.1

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52204

AN:

151946

Hom.:

9375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.316

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.344

AC:

52239

AN:

152064

Hom.:

9382

Cov.:

AF XY:

0.346

AC XY:

25733

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.427

AC:

17707

AN:

41486

American (AMR)

AF:

0.339

AC:

5182

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

905

AN:

3462

East Asian (EAS)

AF:

0.498

AC:

2580

AN:

5182

South Asian (SAS)

AF:

0.326

AC:

1569

AN:

4810

European-Finnish (FIN)

AF:

0.331

AC:

3490

AN:

10556

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.293

AC:

19899

AN:

67982

Other (OTH)

AF:

0.314

AC:

663

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1706

3412

5118

6824

8530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.273

Hom.:

1648

Bravo

AF:

0.347

Asia WGS

AF:

0.398

AC:

1382

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

7.5

(source)

DANN

Benign

0.76

PhyloP100

0.015

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over