9-137139197-AGCC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_007327.4(GRIN1):c.-273_-271del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 157,670 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 32)
  • Exomes 𝑓: 0.010 (0 hom.)
• Consequence: GRIN1 NM_007327.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.299

Genes affected

GRIN1 (HGNC:4584): (glutamate ionotropic receptor NMDA type subunit 1) The protein encoded by this gene is a critical subunit of N-methyl-D-aspartate receptors, members of the glutamate receptor channel superfamily which are heteromeric protein complexes with multiple subunits arranged to form a ligand-gated ion channel. These subunits play a key role in the plasticity of synapses, which is believed to underlie memory and learning. Cell-specific factors are thought to control expression of different isoforms, possibly contributing to the functional diversity of the subunits. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-137139197-AGCC-A is Benign according to our data. Variant chr9-137139197-AGCC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1198978.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00264 (401/151664) while in subpopulation EAS AF= 0.00816 (42/5148). AF 95% confidence interval is 0.0062. There are 3 homozygotes in gnomad4. There are 247 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN1	NM_007327.4	c.-273_-271del		5_prime_UTR_variant	1/20	ENST00000371561.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN1	ENST00000371561.8	c.-273_-271del		5_prime_UTR_variant	1/20	1	NM_007327.4
GRIN1	ENST00000371553.8	c.-273_-271del		5_prime_UTR_variant	1/21	1
GRIN1	ENST00000371560.5	c.-273_-271del		5_prime_UTR_variant	1/20	1		P3
GRIN1	ENST00000350902.9	c.-273_-271del		5_prime_UTR_variant, NMD_transcript_variant	1/19	1

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 401 AN: 151558 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00813

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000752

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.0102 AC: 61 AN: 6006 Hom.: 0 AF XY: 0.0105 AC XY: 37 AN XY: 3518

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0102

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0278

Gnomad4 SAS exome AF: 0.00346

Gnomad4 FIN exome AF: 0.0360

Gnomad4 NFE exome AF: 0.00753

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00264 AC: 401 AN: 151664 Hom.: 3 Cov.: 32 AF XY: 0.00333 AC XY: 247 AN XY: 74122

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00816

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0235

Gnomad4 NFE AF: 0.000752

Gnomad4 OTH AF: 0.000474

Bravo AF: 0.00103

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs763024426; hg19: chr9-140033649;