rs3738399

Positions:

• chr1-231626861-G-A
• chr1-231626861-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018662.3(DISC1):​c.-7G>A variant causes a 5 prime UTR 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 NM_018662.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.-7G>A		5_prime_UTR_variant	1/13	ENST00000439617.8	NP_061132.2
TSNAX-DISC1	NR_028393.1	n.788+9955G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.-7G>A		5_prime_UTR_variant	1/13	5	NM_018662.3	ENSP00000403888	A2

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

GnomAD3 exomes AF: 0.0535 AC: 2959 AN: 55326 Hom.: 225 AF XY: 0.0535 AC XY: 1703 AN XY: 31860

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 SAS exome AF: 0.0983

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

Gnomad4 AFR exome AF: 0.00968

Gnomad4 AMR exome AF: 0.0371

Gnomad4 ASJ exome AF: 0.0318

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.0855

Gnomad4 FIN exome AF: 0.0140

Gnomad4 NFE exome AF: 0.00547

Gnomad4 OTH exome AF: 0.0275

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

Gnomad4 AFR AF: 0.00993

Gnomad4 AMR AF: 0.0232

Gnomad4 ASJ AF: 0.0289

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.0911

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.00648

Gnomad4 OTH AF: 0.0218

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs3738399; hg19: chr1-231762607;