rs1411771

Variant names:

• chr1-232039029-T-C
• rs1411771
• NM_018662.3:c.*2198T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018662.3(DISC1):​c.*2198T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,138 control chromosomes in the GnomAD database, including 10,705 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 0.36 (10705 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DISC1 NM_018662.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.*2198T>C		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.*2198T>C		3_prime_UTR_variant	Exon 13 of 13	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.*2198T>C		3_prime_UTR_variant	Exon 13 of 13	5		ENSP00000355597.6
DISC1	ENST00000622252.4	c.*3304T>C		3_prime_UTR_variant	Exon 12 of 12	5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54431 AN: 152020 Hom.: 10693 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.345

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

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) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.358 AC: 54492 AN: 152138 Hom.: 10705 Cov.: 32 AF XY: 0.354 AC XY: 26291 AN XY: 74366

African (AFR) AF: 0.521 AC: 21598 AN: 41486

American (AMR) AF: 0.312 AC: 4770 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 964 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1723 AN: 5166

South Asian (SAS) AF: 0.261 AC: 1257 AN: 4820

European-Finnish (FIN) AF: 0.302 AC: 3200 AN: 10580

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.290 AC: 19750 AN: 68006

Other (OTH) AF: 0.344 AC: 728 AN: 2114

Alfa AF: 0.318 Hom.: 23144

Bravo AF: 0.370

Asia WGS AF: 0.337 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.25
PhyloP100		-1.8
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: rs1411771; hg19: chr1-232174775;