chr6-100447468-C-T

Variant summary

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

The NM_005068.3(SIM1):​c.851-53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 1,608,336 control chromosomes in the GnomAD database, including 608,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.89 ( 60476 hom., cov: 33)
Exomes 𝑓: 0.87 ( 548114 hom. )

Consequence

SIM1
NM_005068.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.958
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 6-100447468-C-T is Benign according to our data. Variant chr6-100447468-C-T is described in ClinVar as [Benign]. Clinvar id is 1246865.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIM1NM_005068.3 linkc.851-53G>A intron_variant Intron 8 of 11 ENST00000369208.8 NP_005059.2 P81133
SIM1NM_001374769.1 linkc.851-53G>A intron_variant Intron 8 of 11 NP_001361698.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIM1ENST00000369208.8 linkc.851-53G>A intron_variant Intron 8 of 11 1 NM_005068.3 ENSP00000358210.4 P81133
SIM1ENST00000262901.4 linkc.851-53G>A intron_variant Intron 7 of 10 1 ENSP00000262901.4 P81133

Frequencies

GnomAD3 genomes
AF:
0.890
AC:
135367
AN:
152136
Hom.:
60426
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.949
Gnomad AMI
AF:
0.809
Gnomad AMR
AF:
0.892
Gnomad ASJ
AF:
0.745
Gnomad EAS
AF:
0.978
Gnomad SAS
AF:
0.937
Gnomad FIN
AF:
0.882
Gnomad MID
AF:
0.763
Gnomad NFE
AF:
0.854
Gnomad OTH
AF:
0.859
GnomAD4 exome
AF:
0.867
AC:
1262165
AN:
1456082
Hom.:
548114
AF XY:
0.867
AC XY:
628005
AN XY:
723972
show subpopulations
Gnomad4 AFR exome
AF:
0.949
Gnomad4 AMR exome
AF:
0.922
Gnomad4 ASJ exome
AF:
0.742
Gnomad4 EAS exome
AF:
0.981
Gnomad4 SAS exome
AF:
0.937
Gnomad4 FIN exome
AF:
0.877
Gnomad4 NFE exome
AF:
0.855
Gnomad4 OTH exome
AF:
0.866
GnomAD4 genome
AF:
0.890
AC:
135467
AN:
152254
Hom.:
60476
Cov.:
33
AF XY:
0.893
AC XY:
66467
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.949
Gnomad4 AMR
AF:
0.892
Gnomad4 ASJ
AF:
0.745
Gnomad4 EAS
AF:
0.978
Gnomad4 SAS
AF:
0.937
Gnomad4 FIN
AF:
0.882
Gnomad4 NFE
AF:
0.854
Gnomad4 OTH
AF:
0.851
Alfa
AF:
0.855
Hom.:
70258
Bravo
AF:
0.892
Asia WGS
AF:
0.931
AC:
3237
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Nov 12, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
4.1
DANN
Benign
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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.

Other links and lift over

dbSNP: rs397662; hg19: chr6-100895344; COSMIC: COSV53492376; API