rs780102

Variant names:

• chr2-27436624-T-A
• rs780102
• NM_013392.4:c.662-129T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-27436624-T-A
• chr2-27436624-T-C

Variant summary

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

The NM_013392.4(NRBP1):​c.662-129T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000177 in 565,124 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: NRBP1 NM_013392.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 0 publications found

Genes affected

NRBP1 (HGNC:7993): (nuclear receptor binding protein 1) Predicted to enable protein homodimerization activity. Involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Located in endomembrane system. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013392.4. 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
	NRBP1	NM_013392.4	MANE Select	c.662-129T>A		intron	N/A	NP_037524.1
	NRBP1	NM_001321358.2		c.686-129T>A		intron	N/A	NP_001308287.1
	NRBP1	NM_001321359.2		c.686-129T>A		intron	N/A	NP_001308288.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRBP1	ENST00000379852.8	TSL:1 MANE Select	c.662-129T>A		intron	N/A	ENSP00000369181.3
	NRBP1	ENST00000460499.5	TSL:2	n.1043T>A		non_coding_transcript_exon	Exon 1 of 11
	NRBP1	ENST00000379863.7	TSL:5	c.686-129T>A		intron	N/A	ENSP00000369192.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000177 AC: 1 AN: 565124 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 301968

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16150

American (AMR) AF: 0.00 AC: 0 AN: 31832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17570

East Asian (EAS) AF: 0.00 AC: 0 AN: 33480

South Asian (SAS) AF: 0.00 AC: 0 AN: 57852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3904

European-Non Finnish (NFE) AF: 0.00000301 AC: 1 AN: 332046

Other (OTH) AF: 0.00 AC: 0 AN: 30420

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.42
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs780102; hg19: chr2-27659491;