Variant rs3830139 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005068.3(SIM1):c.743+66A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,518,488 control chromosomes in the GnomAD database, including 56,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 5383 hom., cov: 33)

Exomes 𝑓: 0.27 ( 51297 hom. )

Consequence

SIM1
NM_005068.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.336

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 6-100448413-T-G is Benign according to our data. Variant chr6-100448413-T-G is described in ClinVar as [Benign]. Clinvar id is 1246330.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIM1	NM_005068.3 linkuse as main transcript	c.743+66A>C		intron_variant		ENST00000369208.8	NP_005059.2
SIM1	NM_001374769.1 linkuse as main transcript	c.743+66A>C		intron_variant			NP_001361698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8 linkuse as main transcript	c.743+66A>C		intron_variant		1	NM_005068.3	ENSP00000358210	P1
SIM1	ENST00000262901.4 linkuse as main transcript	c.743+66A>C		intron_variant		1		ENSP00000262901	P1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39208

AN:

151998

Hom.:

5380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.244

GnomAD4 exome

AF:

0.269

AC:

368171

AN:

1366372

Hom.:

51297

Cov.:

AF XY:

0.267

AC XY:

181044

AN XY:

677388

show subpopulations

Gnomad4 AFR exome

AF:

0.186

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.212

Gnomad4 EAS exome

AF:

0.429

Gnomad4 SAS exome

AF:

0.212

Gnomad4 FIN exome

AF:

0.311

Gnomad4 NFE exome

AF:

0.265

Gnomad4 OTH exome

AF:

0.266

GnomAD4 genome

AF:

0.258

AC:

39227

AN:

152116

Hom.:

5383

Cov.:

AF XY:

0.263

AC XY:

19562

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.189

Gnomad4 AMR

AF:

0.348

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.400

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.323

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.256

Hom.:

813

Bravo

AF:

0.262

Asia WGS

AF:

0.280

AC:

974

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

8.1

DANN

Benign

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over