chr1-231626861-G-A

Variant names:

• chr1-231626861-G-A
• rs3738399
• ENST00000422590.6:n.-7G>A

Variant summary

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

The ENST00000422590.6(DISC1):​n.-7G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,449,772 control chromosomes in the GnomAD database, including 1,515 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 0.020 (147 hom., cov: 31)
  • Exomes 𝑓: 0.017 (1368 hom.)
• Consequence: DISC1 ENST00000422590.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• Publications: 6 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 = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422590.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.-7G>A		5_prime_UTR	Exon 1 of 13	NP_061132.2
	DISC1	NM_001164537.2		c.-7G>A		5_prime_UTR	Exon 1 of 14	NP_001158009.1
	DISC1	NM_001012957.2		c.-7G>A		5_prime_UTR	Exon 1 of 13	NP_001012975.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000422590.6	TSL:1	n.-7G>A		non_coding_transcript_exon	Exon 1 of 11	ENSP00000415147.2
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.-7G>A		5_prime_UTR	Exon 1 of 13	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.-7G>A		5_prime_UTR	Exon 1 of 13	ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3032 AN: 151836 Hom.: 143 Cov.: 31

Gnomad AFR AF: 0.00998

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0227

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.00648

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.0535 AC: 2959 AN: 55326 AF XY: 0.0535

Gnomad AFR exome AF: 0.0171

Gnomad AMR exome AF: 0.0436

Gnomad ASJ exome AF: 0.0399

Gnomad EAS exome AF: 0.252

Gnomad FIN exome AF: 0.0196

Gnomad NFE exome AF: 0.00824

Gnomad OTH exome AF: 0.0486

GnomAD4 exome AF: 0.0174 AC: 22565 AN: 1297824 Hom.: 1368 Cov.: 30 AF XY: 0.0193 AC XY: 12297 AN XY: 638246

African (AFR) AF: 0.00968 AC: 244 AN: 25194

American (AMR) AF: 0.0371 AC: 708 AN: 19058

Ashkenazi Jewish (ASJ) AF: 0.0318 AC: 639 AN: 20088

East Asian (EAS) AF: 0.237 AC: 7521 AN: 31668

South Asian (SAS) AF: 0.0855 AC: 5735 AN: 67046

European-Finnish (FIN) AF: 0.0140 AC: 443 AN: 31690

Middle Eastern (MID) AF: 0.0211 AC: 78 AN: 3698

European-Non Finnish (NFE) AF: 0.00547 AC: 5720 AN: 1045688

Other (OTH) AF: 0.0275 AC: 1477 AN: 53694

GnomAD4 genome AF: 0.0200 AC: 3039 AN: 151948 Hom.: 147 Cov.: 31 AF XY: 0.0228 AC XY: 1691 AN XY: 74284

African (AFR) AF: 0.00993 AC: 412 AN: 41496

American (AMR) AF: 0.0232 AC: 354 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0289 AC: 100 AN: 3466

East Asian (EAS) AF: 0.212 AC: 1076 AN: 5074

South Asian (SAS) AF: 0.0911 AC: 439 AN: 4820

European-Finnish (FIN) AF: 0.0160 AC: 169 AN: 10578

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 290

European-Non Finnish (NFE) AF: 0.00648 AC: 440 AN: 67912

Other (OTH) AF: 0.0218 AC: 46 AN: 2112

Alfa AF: 0.0126 Hom.: 6

Bravo AF: 0.0211

Asia WGS AF: 0.153 AC: 529 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.83
PhyloP100		-0.67
PromoterAI		0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=300/0	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: rs3738399; hg19: chr1-231762607; COSMIC: COSV107325596; COSMIC: COSV107325596;