rs112509970

Variant names:

• chr17-40344694-C-A
• rs112509970
• NM_000964.4:c.179-3622C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-40344694-C-A
• chr17-40344694-C-T

Variant summary

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

The NM_000964.4(RARA):​c.179-3622C>A 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RARA NM_000964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 0 publications found

Genes affected

RARA (HGNC:9864): (retinoic acid receptor alpha) This gene represents a nuclear retinoic acid receptor. The encoded protein, retinoic acid receptor alpha, regulates transcription in a ligand-dependent manner. This gene has been implicated in regulation of development, differentiation, apoptosis, granulopoeisis, and transcription of clock genes. Translocations between this locus and several other loci have been associated with acute promyelocytic leukemia. Alternatively spliced transcript variants have been found for this locus.[provided by RefSeq, Sep 2010]

RARA Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• acute promyelocytic leukemia

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

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=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000964.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARA	NM_000964.4	MANE Select	c.179-3622C>A		intron	N/A	NP_000955.1	P10276-1
	RARA	NM_001145301.3		c.179-3622C>A		intron	N/A	NP_001138773.1	Q6I9R7
	RARA	NM_001024809.4		c.163+1827C>A		intron	N/A	NP_001019980.1	P10276-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARA	ENST00000254066.10	TSL:1 MANE Select	c.179-3622C>A		intron	N/A	ENSP00000254066.5	P10276-1
	RARA	ENST00000394081.7	TSL:1	c.163+1827C>A		intron	N/A	ENSP00000377643.3	P10276-2
	RARA	ENST00000425707.7	TSL:1	c.179-7216C>A		intron	N/A	ENSP00000389993.3	P10276-3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.57
PhyloP100		-0.13

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: rs112509970; hg19: chr17-38500946;