chr6-100430982-A-G

Position:

• chr6-100430982-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.999-10024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,966 control chromosomes in the GnomAD database, including 7,706 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 0.29 (7706 hom., cov: 31)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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:40530): (SIM1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIM1	NM_005068.3	c.999-10024T>C		intron_variant		ENST00000369208.8	NP_005059.2
SIM1-AS1	XR_942815.4	n.1041+3714A>G		intron_variant, non_coding_transcript_variant
SIM1	NM_001374769.1	c.999-10024T>C		intron_variant			NP_001361698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8	c.999-10024T>C		intron_variant		1	NM_005068.3	ENSP00000358210	P1
SIM1	ENST00000262901.4	c.999-10024T>C		intron_variant		1		ENSP00000262901	P1
SIM1-AS1	ENST00000411442.1	n.151+3714A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44657 AN: 151848 Hom.: 7696 Cov.: 31

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.294 AC: 44701 AN: 151966 Hom.: 7706 Cov.: 31 AF XY: 0.295 AC XY: 21891 AN XY: 74278

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.260

Alfa AF: 0.232 Hom.: 869

Bravo AF: 0.316

Asia WGS AF: 0.307 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.6
DANN	Benign	0.77

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: rs3798497; hg19: chr6-100878858;