rs821639

Positions:

• chr1-232014097-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.2307+5048A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,020 control chromosomes in the GnomAD database, including 7,816 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 0.32 (7816 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.2307+5048A>G		intron_variant		ENST00000439617.8	NP_061132.2
TSNAX-DISC1	NR_028393.1	n.2973+5048A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.2307+5048A>G		intron_variant		5	NM_018662.3	ENSP00000403888	A2
DISC1	ENST00000366637.8	c.2241+5114A>G		intron_variant		5		ENSP00000355597	P2
DISC1	ENST00000622252.4	c.*848+5048A>G		intron_variant		5		ENSP00000481791

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47940 AN: 151900 Hom.: 7797 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.284

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.316 AC: 48012 AN: 152020 Hom.: 7816 Cov.: 32 AF XY: 0.318 AC XY: 23613 AN XY: 74296

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.287

Alfa AF: 0.307 Hom.: 14506

Bravo AF: 0.303

Asia WGS AF: 0.269 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.4
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs821639; hg19: chr1-232149843; COSMIC: COSV64093965; COSMIC: COSV64093965;