4-26222167-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The XR_007058094.1(LOC124900690):n.267-9248G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 152,258 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.0039 (2 hom., cov: 32)
• Consequence: LOC124900690 XR_007058094.1 intron, non_coding_transcript
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.53

Genes affected

LOC124900690 (HGNC:):

RBPJ (HGNC:5724): (recombination signal binding protein for immunoglobulin kappa J region) The protein encoded by this gene is a transcriptional regulator important in the Notch signaling pathway. The encoded protein acts as a repressor when not bound to Notch proteins and an activator when bound to Notch proteins. It is thought to function by recruiting chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins to Notch signaling pathway genes. Several transcript variants encoding different isoforms have been found for this gene, and several pseudogenes of this gene exist on chromosome 9. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BP6: Variant 4-26222167-C-T is Benign according to our data. Variant chr4-26222167-C-T is described in ClinVar as [Benign]. Clinvar id is 444123.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124900690	XR_007058094.1	n.267-9248G>A		intron_variant, non_coding_transcript_variant
RBPJ	NM_001374401.1	c.-167+58553C>T		intron_variant
RBPJ	XM_047415656.1	c.77+58553C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBPJ	ENST00000512351.5	c.-167+58553C>T		intron_variant		4
RBPJ	ENST00000681799.1	c.-264-41450C>T		intron_variant, NMD_transcript_variant
RBPJ	ENST00000681403.1	n.85+58553C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00390 AC: 594 AN: 152140 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00509

Gnomad OTH AF: 0.00287

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

GnomAD4 genome AF: 0.00390 AC: 594 AN: 152258 Hom.: 2 Cov.: 32 AF XY: 0.00333 AC XY: 248 AN XY: 74442

Gnomad4 AFR AF: 0.00154

Gnomad4 AMR AF: 0.00981

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00509

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00448 Hom.: 0

Bravo AF: 0.00488

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Type 2 diabetes mellitus Benign:1

Benign, no assertion criteria provided

case-control

Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institutes of Health

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.13
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs114530054; hg19: chr4-26223789;