1-151811212-A-T

Variant names:

• chr1-151811212-A-T
• rs939595
• NM_005060.4:c.1395+113T>A

Variant summary

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

The NM_005060.4(RORC):​c.1395+113T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 448,396 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: 0.000022 (0 hom.)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.91
• Publications: 16 publications found

Genes affected

RORC (HGNC:10260): (RAR related orphan receptor C) The protein encoded by this gene is a DNA-binding transcription factor and is a member of the NR1 subfamily of nuclear hormone receptors. The specific functions of this protein are not known; however, studies of a similar gene in mice have shown that this gene may be essential for lymphoid organogenesis and may play an important regulatory role in thymopoiesis. In addition, studies in mice suggest that the protein encoded by this gene may inhibit the expression of Fas ligand and IL2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RORC Gene-Disease associations (from GenCC):

• autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

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=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORC	NM_005060.4	c.1395+113T>A		intron_variant	Intron 10 of 10	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.1332+113T>A		intron_variant	Intron 9 of 9		NP_001001523.1
RORC	XM_006711484.5	c.1557+113T>A		intron_variant	Intron 11 of 11		XP_006711547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7	c.1395+113T>A		intron_variant	Intron 10 of 10	1	NM_005060.4	ENSP00000327025.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000223 AC: 10 AN: 448396 Hom.: 0 AF XY: 0.0000212 AC XY: 5 AN XY: 235732

African (AFR) AF: 0.0000748 AC: 1 AN: 13370

American (AMR) AF: 0.00 AC: 0 AN: 20642

Ashkenazi Jewish (ASJ) AF: 0.000305 AC: 4 AN: 13136

East Asian (EAS) AF: 0.0000308 AC: 1 AN: 32456

South Asian (SAS) AF: 0.0000249 AC: 1 AN: 40212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2104

European-Non Finnish (NFE) AF: 0.00000763 AC: 2 AN: 261980

Other (OTH) AF: 0.0000398 AC: 1 AN: 25112

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 80563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.011
DANN	Benign	0.21
PhyloP100		-2.9

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: rs939595; hg19: chr1-151783688;