rs77633370

Variant names:

• chr17-40354331-C-A
• rs77633370
• NM_000964.4:c.837C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-40354331-C-A
• chr17-40354331-C-G
• chr17-40354331-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000964.4(RARA):​c.837C>A​(p.Pro279Pro) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. P279P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RARA NM_000964.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33
• Publications: 7 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=-3.33 with no splicing effect.

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.837C>A	p.Pro279Pro	synonymous	Exon 7 of 9	NP_000955.1	P10276-1
	RARA	NM_001145301.3		c.837C>A	p.Pro279Pro	synonymous	Exon 7 of 9	NP_001138773.1	Q6I9R7
	RARA	NM_001024809.4		c.822C>A	p.Pro274Pro	synonymous	Exon 6 of 8	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.837C>A	p.Pro279Pro	synonymous	Exon 7 of 9	ENSP00000254066.5	P10276-1
	RARA	ENST00000394081.7	TSL:1	c.822C>A	p.Pro274Pro	synonymous	Exon 6 of 8	ENSP00000377643.3	P10276-2
	RARA	ENST00000425707.7	TSL:1	c.546C>A	p.Pro182Pro	synonymous	Exon 5 of 7	ENSP00000389993.3	P10276-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	6.8
DANN	Benign	0.72
PhyloP100		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs77633370; hg19: chr17-38510583;