6-100443115-A-G

Position:

• chr6-100443115-A-G

Variant summary

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

The NM_005068.3(SIM1):​c.998+4153T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,658 control chromosomes in the GnomAD database, including 13,595 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 0.40 (13595 hom., cov: 32)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIM1	NM_005068.3	c.998+4153T>C		intron_variant		ENST00000369208.8	NP_005059.2
SIM1	NM_001374769.1	c.998+4153T>C		intron_variant			NP_001361698.1
SIM1-AS1	NR_187148.1	n.6901A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8	c.998+4153T>C		intron_variant		1	NM_005068.3	ENSP00000358210.4
SIM1	ENST00000262901.4	c.998+4153T>C		intron_variant		1		ENSP00000262901.4

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61255 AN: 151540 Hom.: 13569 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.404 AC: 61328 AN: 151658 Hom.: 13595 Cov.: 32 AF XY: 0.408 AC XY: 30232 AN XY: 74118

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.351

Alfa AF: 0.336 Hom.: 1486

Bravo AF: 0.426

Asia WGS AF: 0.437 AC: 1513 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.0
DANN	Benign	0.78

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: rs241812; hg19: chr6-100890991;