dbSNP rs17241549: SIM1:c.1167+4386G>C (chr6-100416404-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005068.3(SIM1):c.1167+4386G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 152,156 control chromosomes in the GnomAD database, including 286 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 0.055 ( 286 hom., cov: 32)

Consequence

SIM1
NM_005068.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.107

Publications

2 publications found

Variant links:

Genes affected

SIM1 (HGNC:10882): (SIM bHLH transcription factor 1) SIM1 and SIM2 genes are Drosophila single-minded (sim) gene homologs. SIM1 transcript was detected only in fetal kidney out of various adult and fetal tissues tested. Since the sim gene plays an important role in Drosophila development and has peak levels of expression during the period of neurogenesis,it was proposed that the human SIM gene is a candidate for involvement in certain dysmorphic features (particularly the facial and skull characteristics), abnormalities of brain development, and/or cognitive disability of Down syndrome. [provided by RefSeq, Jul 2008]

SIM1 links:

SIM1-AS1 (HGNC:40530): (SIM1 antisense RNA 1)

SIM1-AS1 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0687 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005068.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIM1	NM_005068.3	MANE Select	c.1167+4386G>C	intron	N/A	NP_005059.2
SIM1	NM_001374769.1		c.1167+4386G>C	intron	N/A	NP_001361698.1	P81133
SIM1-AS1	NR_187148.1		n.891-10714C>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIM1	ENST00000369208.8	TSL:1 MANE Select	c.1167+4386G>C	intron	N/A	ENSP00000358210.4	P81133
SIM1	ENST00000262901.4	TSL:1	c.1167+4386G>C	intron	N/A	ENSP00000262901.4	P81133
SIM1	ENST00000900753.1		c.1167+4386G>C	intron	N/A	ENSP00000570812.1

Frequencies

GnomAD3 genomes

AF:

0.0548

AC:

8325

AN:

152036

Hom.:

286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0363

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0377

Gnomad ASJ

AF:

0.0802

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0418

Gnomad FIN

AF:

0.0718

Gnomad MID

AF:

0.0669

Gnomad NFE

AF:

0.0703

Gnomad OTH

AF:

0.0507

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

GnomAD4 genome

AF:

0.0547

AC:

8326

AN:

152156

Hom.:

286

Cov.:

AF XY:

0.0547

AC XY:

4066

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0362

AC:

1504

AN:

41538

American (AMR)

AF:

0.0376

AC:

575

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0802

AC:

278

AN:

3468

East Asian (EAS)

AF:

0.00116

AC:

AN:

5180

South Asian (SAS)

AF:

0.0420

AC:

203

AN:

4828

European-Finnish (FIN)

AF:

0.0718

AC:

759

AN:

10564

Middle Eastern (MID)

AF:

0.0651

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0704

AC:

4783

AN:

67978

Other (OTH)

AF:

0.0501

AC:

106

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

411

822

1233

1644

2055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0625

Hom.:

Bravo

AF:

0.0513

Asia WGS

AF:

0.0190

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.8

(source)

DANN

Benign

0.59

PhyloP100

-0.11

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

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