rs12044355

Variant names:

• chr1-231708601-A-C
• rs12044355
• NM_018662.3:c.1117+6577A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-231708601-A-C
• chr1-231708601-A-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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:49177): (TSNAX-DISC1 readthrough (NMD candidate)) This gene represents naturally occurring read-through transcription between the neighboring TSNAX (translin-associated factor X) and DISC1 (disrupted in schizophrenia 1) genes on chromosome 1. Alternative splicing results in multiple transcript variants, all of which are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to be protein-coding. These alterations in gene processing may be associated with risk for psychiatric illness, most notably, schizophrenia. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1117+6577A>C		intron_variant	Intron 3 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1117+6577A>C		intron_variant	Intron 3 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1117+6577A>C		intron_variant	Intron 3 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*978+6577A>C		intron_variant	Intron 7 of 12	2		ENSP00000473532.1

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

African (AFR) AF: 0.142 AC: 5880 AN: 41524

American (AMR) AF: 0.323 AC: 4935 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1050 AN: 3468

East Asian (EAS) AF: 0.372 AC: 1914 AN: 5146

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4820

European-Finnish (FIN) AF: 0.315 AC: 3320 AN: 10556

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23351 AN: 67978

Other (OTH) AF: 0.333 AC: 703 AN: 2108

Alfa AF: 0.326 Hom.: 27930

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
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12044355; hg19: chr1-231844347;