chr1-232041451-A-G

Variant names:

• chr1-232041451-A-G
• rs17773946
• NM_018662.3:c.*4620A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_018662.3(DISC1):​c.*4620A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 152,308 control chromosomes in the GnomAD database, including 91 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 0.029 (91 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.029 (4410/152308) while in subpopulation NFE AF= 0.0409 (2785/68028). AF 95% confidence interval is 0.0397. There are 91 homozygotes in gnomad4. There are 2268 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 91 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.*4620A>G		downstream_gene_variant		ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.*4620A>G		downstream_gene_variant		5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000622252.4	c.*5726A>G		downstream_gene_variant		5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4411 AN: 152190 Hom.: 91 Cov.: 33

Gnomad AFR AF: 0.00712

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0805

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0409

Gnomad OTH AF: 0.0244

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

GnomAD4 genome AF: 0.0290 AC: 4410 AN: 152308 Hom.: 91 Cov.: 33 AF XY: 0.0305 AC XY: 2268 AN XY: 74474

Gnomad4 AFR AF: 0.00710

Gnomad4 AMR AF: 0.0223

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0805

Gnomad4 NFE AF: 0.0409

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0349 Hom.: 12

Bravo AF: 0.0234

Asia WGS AF: 0.00231 AC: 8 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	2.0
DANN	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17773946; hg19: chr1-232177197;