rs17241549

Positions:

• chr6-100416404-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIM1	NM_005068.3	c.1167+4386G>C		intron_variant		ENST00000369208.8	NP_005059.2
SIM1-AS1	XR_942815.4	n.891-10714C>G		intron_variant, non_coding_transcript_variant
SIM1	NM_001374769.1	c.1167+4386G>C		intron_variant			NP_001361698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8	c.1167+4386G>C		intron_variant		1	NM_005068.3	ENSP00000358210	P1
SIM1	ENST00000262901.4	c.1167+4386G>C		intron_variant		1		ENSP00000262901	P1

Frequencies

GnomAD3 genomes AF: 0.0548 AC: 8325 AN: 152036 Hom.: 286 Cov.: 32

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.: 32 AF XY: 0.0547 AC XY: 4066 AN XY: 74348

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.0376

Gnomad4 ASJ AF: 0.0802

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0420

Gnomad4 FIN AF: 0.0718

Gnomad4 NFE AF: 0.0704

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0625 Hom.: 48

Bravo AF: 0.0513

Asia WGS AF: 0.0190 AC: 67 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs17241549; hg19: chr6-100864280;