1-51243111-A-G

Position:

• chr1-51243111-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014372.5(RNF11):​c.123+6232A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,164 control chromosomes in the GnomAD database, including 3,111 homozygotes. 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: 𝑓 0.16 (3111 hom., cov: 32)
• Consequence: RNF11 NM_014372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

Genes affected

RNF11 (HGNC:10056): (ring finger protein 11) The protein encoded by this gene contains a RING-H2 finger motif, which is known to be important for protein-protein interactions. The expression of this gene has been shown to be induced by mutant RET proteins (MEN2A/MEN2B). The germline mutations in RET gene are known to be responsible for the development of multiple endocrine neoplasia (MEN). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF11	NM_014372.5	c.123+6232A>G		intron_variant		ENST00000242719.4	NP_055187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF11	ENST00000242719.4	c.123+6232A>G		intron_variant		1	NM_014372.5	ENSP00000242719	P1
RNF11	ENST00000494873.1	n.541+6232A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24381 AN: 152046 Hom.: 3078 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0990

Gnomad SAS AF: 0.0799

Gnomad FIN AF: 0.0564

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.161 AC: 24461 AN: 152164 Hom.: 3111 Cov.: 32 AF XY: 0.157 AC XY: 11658 AN XY: 74402

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.0906

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.0991

Gnomad4 SAS AF: 0.0793

Gnomad4 FIN AF: 0.0564

Gnomad4 NFE AF: 0.0876

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0688 Hom.: 127

Bravo AF: 0.173

Asia WGS AF: 0.154 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs7526029; hg19: chr1-51708783;