rs9661837

Positions:

• chr1-232039192-A-G

Variant summary

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

The NM_018662.3(DISC1):​c.*2361A>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 0.0289 in 152,304 control chromosomes in the GnomAD database, including 220 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 (220 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DISC1 NM_018662.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.805

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.*2361A>G		3_prime_UTR_variant	13/13	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.*2361A>G		3_prime_UTR_variant	13/13	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.*2361A>G		3_prime_UTR_variant	13/13	5		ENSP00000355597.6
DISC1	ENST00000622252.4	c.*3467A>G		3_prime_UTR_variant	12/12	5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4384 AN: 152186 Hom.: 221 Cov.: 32

Gnomad AFR AF: 0.0981

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0127

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.0206

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

GnomAD4 genome AF: 0.0289 AC: 4403 AN: 152304 Hom.: 220 Cov.: 32 AF XY: 0.0281 AC XY: 2090 AN XY: 74482

Gnomad4 AFR AF: 0.0982

Gnomad4 AMR AF: 0.0127

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0177 Hom.: 28

Bravo AF: 0.0330

Asia WGS AF: 0.00664 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9661837; hg19: chr1-232174938;