rs999710

Variant names:

• chr1-231875197-G-A
• rs999710
• NM_018662.3:c.1981+56680G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-231875197-G-A
• chr1-231875197-G-C
• chr1-231875197-G-T

Variant summary

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

The NM_018662.3(DISC1):​c.1981+56680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,042 control chromosomes in the GnomAD database, including 11,485 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 0.38 (11485 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1981+56680G>A		intron_variant	Intron 9 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1981+56680G>A		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1981+56680G>A		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58487 AN: 151924 Hom.: 11476 Cov.: 31

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.385 AC: 58524 AN: 152042 Hom.: 11485 Cov.: 31 AF XY: 0.388 AC XY: 28817 AN XY: 74320

African (AFR) AF: 0.332 AC: 13764 AN: 41476

American (AMR) AF: 0.401 AC: 6120 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1278 AN: 3472

East Asian (EAS) AF: 0.511 AC: 2642 AN: 5166

South Asian (SAS) AF: 0.413 AC: 1993 AN: 4820

European-Finnish (FIN) AF: 0.442 AC: 4668 AN: 10558

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26790 AN: 67950

Other (OTH) AF: 0.399 AC: 844 AN: 2114

Alfa AF: 0.258 Hom.: 656

Bravo AF: 0.379

Asia WGS AF: 0.473 AC: 1643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.59
PhyloP100		-0.36
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: rs999710; hg19: chr1-232010943; COSMIC: COSV64093585;