rs56073218

Variant names:

• chr15-45433057-C-G
• rs56073218
• NM_197955.3:c.*41C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-45433057-C-G
• chr15-45433057-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_197955.3(COXFA4L3):​c.*41C>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00131 in 1,548,228 control chromosomes in the GnomAD database, including 2 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 0.00093 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (1 hom.)
• Consequence: COXFA4L3 NM_197955.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• Publications: 6 publications found

Genes affected

COXFA4L3 (HGNC:29898): (chromosome 15 open reading frame 48) This gene was first identified in a study of human esophageal squamous cell carcinoma tissues. Levels of both the message and protein are reduced in carcinoma samples. In adult human tissues, this gene is expressed in the the esophagus, stomach, small intestine, colon and placenta. Alternatively spliced transcript variants that encode the same protein have been identified. [provided by RefSeq, Jun 2012]

MIR147B (HGNC:33655): (microRNA 147b) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ENSG00000259342 (HGNC:56076):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197955.3. 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
	COXFA4L3	NM_197955.3	MANE Select	c.*41C>G		3_prime_UTR	Exon 5 of 5	NP_922946.1
	COXFA4L3	NM_032413.4		c.*41C>G		3_prime_UTR	Exon 4 of 4	NP_115789.1
	MIR147B	NR_030599.1		n.8C>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C15orf48	ENST00000396650.7	TSL:1 MANE Select	c.*41C>G		3_prime_UTR	Exon 5 of 5	ENSP00000379887.2	Q9C002
	C15orf48	ENST00000344300.3	TSL:1	c.*41C>G		3_prime_UTR	Exon 4 of 4	ENSP00000341610.3	Q9C002
	C15orf48	ENST00000960373.1		c.*41C>G		3_prime_UTR	Exon 5 of 5	ENSP00000630432.1

Frequencies

GnomAD3 genomes AF: 0.000929 AC: 141 AN: 151856 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000315

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000570

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000859 AC: 216 AN: 251346 AF XY: 0.000868

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.00123

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.00135 AC: 1881 AN: 1396254 Hom.: 1 Cov.: 24 AF XY: 0.00135 AC XY: 940 AN XY: 698452

African (AFR) AF: 0.000251 AC: 8 AN: 31904

American (AMR) AF: 0.000247 AC: 11 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25740

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39350

South Asian (SAS) AF: 0.00130 AC: 110 AN: 84842

European-Finnish (FIN) AF: 0.000637 AC: 34 AN: 53364

Middle Eastern (MID) AF: 0.000354 AC: 2 AN: 5648

European-Non Finnish (NFE) AF: 0.00157 AC: 1651 AN: 1052570

Other (OTH) AF: 0.00110 AC: 64 AN: 58224

GnomAD4 genome AF: 0.000928 AC: 141 AN: 151974 Hom.: 1 Cov.: 33 AF XY: 0.000862 AC XY: 64 AN XY: 74286

African (AFR) AF: 0.000314 AC: 13 AN: 41446

American (AMR) AF: 0.0000656 AC: 1 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4826

European-Finnish (FIN) AF: 0.000570 AC: 6 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00160 AC: 109 AN: 67994

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000974 Hom.: 0

Bravo AF: 0.000869

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.87
PhyloP100		3.7
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs56073218;

hg19: chr15-45725255;