rs12044355

chr1-231708601-A-Cchr1-231708601-A-G

Variant summary

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

The NM_018662.3(DISC1):c.1117+6577A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,080 control chromosomes in the GnomAD database, including 6,702 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 0.28 (6702 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448

Genes affected

DISC1 (HGNC:2888): (DISC1 scaffold protein) This gene encodes a protein with multiple coiled coil motifs which is located in the nucleus, cytoplasm and mitochondria. The protein is involved in neurite outgrowth and cortical development through its interaction with other proteins. This gene is disrupted in a t(1;11)(q42.1;q14.3) translocation which segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

TSNAX-DISC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1117+6577A>C		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.1838+6577A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1117+6577A>C		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42868 AN: 151962 Hom.: 6698 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.282 AC: 42872 AN: 152080 Hom.: 6702 Cov.: 32 AF XY: 0.279 AC XY: 20747 AN XY: 74326

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.333

Alfa AF: 0.334 Hom.: 11203

Bravo AF: 0.280

Asia WGS AF: 0.334 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.84
Dann	Benign	0.57

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: rs12044355; hg19: chr1-231844347;