rs11642466

Variant names:

• chr16-30770621-A-G
• rs11642466
• NM_014771.4:c.2586+1021A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014771.4(RNF40):​c.2586+1021A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0695 in 152,316 control chromosomes in the GnomAD database, including 475 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 0.070 (475 hom., cov: 31)
• Consequence: RNF40 NM_014771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• Publications: 17 publications found

Genes affected

RNF40 (HGNC:16867): (ring finger protein 40) The protein encoded by this gene contains a RING finger, a motif known to be involved in protein-protein and protein-DNA interactions. This protein was reported to interact with the tumor suppressor protein RB1. Studies of the rat counterpart suggested that this protein may function as an E3 ubiquitin-protein ligase, and facilitate the ubiquitination and degradation of syntaxin 1, which is an essential component of the neurotransmitter release machinery. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF40	NM_014771.4	c.2586+1021A>G		intron_variant	Intron 17 of 19	ENST00000324685.11	NP_055586.1
RNF40	NM_001286572.3	c.2586+1021A>G		intron_variant	Intron 17 of 19		NP_001273501.1
RNF40	NM_001207033.1	c.2586+1021A>G		intron_variant	Intron 17 of 19		NP_001193962.1
RNF40	NM_001207034.1	c.2286+1021A>G		intron_variant	Intron 15 of 17		NP_001193963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF40	ENST00000324685.11	c.2586+1021A>G		intron_variant	Intron 17 of 19	1	NM_014771.4	ENSP00000325677.6

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 10593 AN: 152198 Hom.: 475 Cov.: 31

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0558

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0702

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

GnomAD4 genome AF: 0.0695 AC: 10588 AN: 152316 Hom.: 475 Cov.: 31 AF XY: 0.0668 AC XY: 4976 AN XY: 74488

African (AFR) AF: 0.0267 AC: 1108 AN: 41570

American (AMR) AF: 0.0558 AC: 853 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.0348 AC: 168 AN: 4826

European-Finnish (FIN) AF: 0.0575 AC: 611 AN: 10620

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7435 AN: 68016

Other (OTH) AF: 0.0695 AC: 147 AN: 2116

Alfa AF: 0.0935 Hom.: 1267

Bravo AF: 0.0680

Asia WGS AF: 0.0160 AC: 54 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	3.0
DANN	Benign	0.59
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs11642466; hg19: chr16-30781942;