chr12-66517991-G-C

Variant names:

• chr12-66517991-G-C
• rs11838180
• NM_001366722.1:c.503-15C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001379345.1(GRIP1):​c.581-15C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRIP1 NM_001379345.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.118
• Publications: 0 publications found

Genes affected

GRIP1 (HGNC:18708): (glutamate receptor interacting protein 1) This gene encodes a member of the glutamate receptor interacting protein family. The encoded scaffold protein binds to and mediates the trafficking and membrane organization of a number of transmembrane proteins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, May 2010]

GRIP1 Gene-Disease associations (from GenCC):

• Fraser syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• Fraser syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-66517991-G-C is Benign according to our data. Variant chr12-66517991-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2835406.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379345.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	NM_001366722.1	MANE Select	c.503-15C>G		intron	N/A	NP_001353651.1
	GRIP1	NM_001379345.1		c.581-15C>G		intron	N/A	NP_001366274.1
	GRIP1	NM_001439322.1		c.506-15C>G		intron	N/A	NP_001426251.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	ENST00000359742.9	TSL:5 MANE Select	c.503-15C>G		intron	N/A	ENSP00000352780.4
	GRIP1	ENST00000398016.7	TSL:1	c.503-15C>G		intron	N/A	ENSP00000381098.3
	GRIP1	ENST00000536215.5	TSL:1	c.335-15C>G		intron	N/A	ENSP00000446011.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.3
DANN	Benign	0.49
PhyloP100		0.12
PromoterAI		-0.0072	Neutral

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: rs11838180; hg19: chr12-66911771;