rs72631820

Positions:

• chr7-1022963-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001318252.2(C7orf50):​c.130-12820A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 472,066 control chromosomes in the GnomAD database, including 64 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 0.013 (21 hom., cov: 33)
  • Exomes 𝑓: 0.0093 (43 hom.)
• Consequence: C7orf50 NM_001318252.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

Genes affected

C7orf50 (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

MIR339 (HGNC:31776): (microRNA 339) 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1922/152344) while in subpopulation AFR AF= 0.0275 (1143/41576). AF 95% confidence interval is 0.0262. There are 21 homozygotes in gnomad4. There are 927 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C7orf50	NM_001318252.2	c.130-12820A>G		intron_variant		ENST00000397098.8	NP_001305181.1
MIR339	NR_029898.1	n.64A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C7orf50	ENST00000397098.8	c.130-12820A>G		intron_variant		1	NM_001318252.2	ENSP00000380286	P1
MIR339	ENST00000362153.3	n.64A>G		mature_miRNA_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1924 AN: 152226 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0196

Gnomad FIN AF: 0.00103

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00595

Gnomad OTH AF: 0.0249

GnomAD3 exomes AF: 0.00921 AC: 1464 AN: 158958 Hom.: 10 AF XY: 0.00995 AC XY: 873 AN XY: 87720

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.00567

Gnomad ASJ exome AF: 0.00908

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0215

Gnomad FIN exome AF: 0.00207

Gnomad NFE exome AF: 0.00622

Gnomad OTH exome AF: 0.00828

GnomAD4 exome AF: 0.00934 AC: 2985 AN: 319722 Hom.: 43 Cov.: 0 AF XY: 0.0107 AC XY: 1955 AN XY: 181866

Gnomad4 AFR exome AF: 0.0273

Gnomad4 AMR exome AF: 0.00580

Gnomad4 ASJ exome AF: 0.00937

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0220

Gnomad4 FIN exome AF: 0.00211

Gnomad4 NFE exome AF: 0.00544

Gnomad4 OTH exome AF: 0.00803

GnomAD4 genome AF: 0.0126 AC: 1922 AN: 152344 Hom.: 21 Cov.: 33 AF XY: 0.0124 AC XY: 927 AN XY: 74496

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.0113

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.00103

Gnomad4 NFE AF: 0.00595

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.00963 Hom.: 3

Bravo AF: 0.0140

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.74

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: rs72631820; hg19: chr7-1062599;