NM_001395907.1:c.1161-5860C>A

Variant names:

• chr14-67215919-C-A
• rs10431718
• NM_001395907.1:c.1161-5860C>A

Variant summary

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

The NM_001395907.1(GARIN2):​c.1161-5860C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,090 control chromosomes in the GnomAD database, including 3,122 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 0.15 (3122 hom., cov: 32)
• Consequence: GARIN2 NM_001395907.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 6 publications found

Genes affected

GARIN2 (HGNC:20101): (golgi associated RAB2 interactor family member 2)

GPHN (HGNC:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]

GPHN Gene-Disease associations (from GenCC):

• sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
• hereditary hyperekplexia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARIN2	NM_001395907.1	c.1161-5860C>A		intron_variant	Intron 6 of 7	ENST00000696955.1	NP_001382836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARIN2	ENST00000696955.1	c.1161-5860C>A		intron_variant	Intron 6 of 7		NM_001395907.1	ENSP00000512992.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22487 AN: 151972 Hom.: 3115 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.148 AC: 22529 AN: 152090 Hom.: 3122 Cov.: 32 AF XY: 0.155 AC XY: 11491 AN XY: 74360

African (AFR) AF: 0.310 AC: 12871 AN: 41472

American (AMR) AF: 0.215 AC: 3276 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 231 AN: 3468

East Asian (EAS) AF: 0.421 AC: 2172 AN: 5162

South Asian (SAS) AF: 0.260 AC: 1251 AN: 4812

European-Finnish (FIN) AF: 0.0538 AC: 571 AN: 10616

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0267 AC: 1812 AN: 67980

Other (OTH) AF: 0.148 AC: 314 AN: 2116

Alfa AF: 0.0878 Hom.: 239

Bravo AF: 0.167

Asia WGS AF: 0.292 AC: 1020 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.25
DANN	Benign	0.63
PhyloP100		-1.6

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: rs10431718; hg19: chr14-67682636;