rs12744221

Variant names:

• chr1-145789475-G-A
• rs12744221
• NM_014455.4:c.103-509C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-145789475-G-A
• chr1-145789475-G-C
• chr1-145789475-G-T

Variant summary

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

The NM_014455.4(RNF115):​c.103-509C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 150,092 control chromosomes in the GnomAD database, including 7,244 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 0.29 (7244 hom., cov: 29)
• Consequence: RNF115 NM_014455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.62
• Publications: 7 publications found

Genes affected

RNF115 (HGNC:18154): (ring finger protein 115) Enables ubiquitin-protein transferase activity. Involved in negative regulation of epidermal growth factor receptor signaling pathway; protein autoubiquitination; and ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF115	NM_014455.4	c.103-509C>T		intron_variant	Intron 1 of 8	ENST00000582693.5	NP_055270.1
RNF115	XM_047418024.1	c.-49-509C>T		intron_variant	Intron 2 of 10		XP_047273980.1
RNF115	XM_047418027.1	c.-82-4879C>T		intron_variant	Intron 1 of 7		XP_047273983.1
RNF115	XM_047418028.1	c.103-509C>T		intron_variant	Intron 1 of 5		XP_047273984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF115	ENST00000582693.5	c.103-509C>T		intron_variant	Intron 1 of 8	1	NM_014455.4	ENSP00000463650.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 43961 AN: 149974 Hom.: 7249 Cov.: 29

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.293 AC: 43963 AN: 150092 Hom.: 7244 Cov.: 29 AF XY: 0.293 AC XY: 21458 AN XY: 73210

African (AFR) AF: 0.144 AC: 5883 AN: 40760

American (AMR) AF: 0.328 AC: 4942 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1015 AN: 3446

East Asian (EAS) AF: 0.158 AC: 800 AN: 5064

South Asian (SAS) AF: 0.251 AC: 1193 AN: 4748

European-Finnish (FIN) AF: 0.400 AC: 4090 AN: 10226

Middle Eastern (MID) AF: 0.204 AC: 57 AN: 280

European-Non Finnish (NFE) AF: 0.369 AC: 24887 AN: 67532

Other (OTH) AF: 0.269 AC: 555 AN: 2066

Alfa AF: 0.324 Hom.: 1114

Bravo AF: 0.279

Asia WGS AF: 0.173 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.043
DANN	Benign	0.71
PhyloP100		-4.6

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: rs12744221; hg19: chr1-145645606;