1-40161432-C-G

Variant names:

• chr1-40161432-C-G
• rs778085294
• NM_012421.4:c.33C>G

Variant summary

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

The NM_012421.4(RLF):​c.33C>G​(p.Val11Val) 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. V11V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RLF NM_012421.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292
• Publications: 0 publications found

Genes affected

RLF (HGNC:10025): (RLF zinc finger) Predicted to enable DNA binding activity and DNA-binding transcription activator activity, RNA polymerase II-specific. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within histone H3-K4 monomethylation and regulation of DNA methylation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000303499 (HGNC:):

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=-0.24).
• BP7: Synonymous conserved (PhyloP=0.292 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012421.4. 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
	RLF	NM_012421.4	MANE Select	c.33C>G	p.Val11Val	synonymous	Exon 1 of 8	NP_036553.2	Q13129

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RLF	ENST00000372771.5	TSL:1 MANE Select	c.33C>G	p.Val11Val	synonymous	Exon 1 of 8	ENSP00000361857.4	Q13129
	ENSG00000303499	ENST00000795129.1		n.-175G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		0.29
PromoterAI		0.020	Neutral
Mutation Taster		=100/0	polymorphism

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: rs778085294; hg19: chr1-40627104;