rs17060530

Positions:

• chr6-100412071-T-C
• chr6-100412071-T-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+8719A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,738 control chromosomes in the GnomAD database, including 11,521 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 0.38 (11521 hom., cov: 30)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIM1	NM_005068.3	c.1167+8719A>G		intron_variant		ENST00000369208.8	NP_005059.2
SIM1	NM_001374769.1	c.1167+8719A>G		intron_variant			NP_001361698.1
SIM1-AS1	NR_187148.1	n.891-15047T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8	c.1167+8719A>G		intron_variant		1	NM_005068.3	ENSP00000358210.4
SIM1	ENST00000262901.4	c.1167+8719A>G		intron_variant		1		ENSP00000262901.4

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58002 AN: 151620 Hom.: 11489 Cov.: 30

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.383 AC: 58089 AN: 151738 Hom.: 11521 Cov.: 30 AF XY: 0.386 AC XY: 28639 AN XY: 74120

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.373

Alfa AF: 0.358 Hom.: 19904

Bravo AF: 0.388

Asia WGS AF: 0.521 AC: 1809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.52

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: rs17060530; hg19: chr6-100859947;