chr1-232039522-A-G

Variant names:

• chr1-232039522-A-G
• rs11122396
• NM_018662.3:c.*2691A>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.*2691A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 152,074 control chromosomes in the GnomAD database, including 426 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 0.061 (426 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DISC1 NM_018662.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.*2691A>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.*2691A>G		3_prime_UTR_variant	Exon 13 of 13	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.*2691A>G		3_prime_UTR_variant	Exon 13 of 13	5		ENSP00000355597.6
DISC1	ENST00000622252.4	c.*3797A>G		3_prime_UTR_variant	Exon 12 of 12	5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9195 AN: 151956 Hom.: 425 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.0392

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0675

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0606 AC: 9216 AN: 152074 Hom.: 426 Cov.: 32 AF XY: 0.0594 AC XY: 4414 AN XY: 74342

African (AFR) AF: 0.110 AC: 4574 AN: 41472

American (AMR) AF: 0.0677 AC: 1034 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 179 AN: 3470

East Asian (EAS) AF: 0.174 AC: 888 AN: 5112

South Asian (SAS) AF: 0.0390 AC: 188 AN: 4822

European-Finnish (FIN) AF: 0.0197 AC: 209 AN: 10588

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0285 AC: 1941 AN: 68016

Other (OTH) AF: 0.0673 AC: 142 AN: 2110

Alfa AF: 0.0409 Hom.: 226

Bravo AF: 0.0680

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.62
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11122396; hg19: chr1-232175268;