rs72631820

Variant names:

• chr7-1022963-T-C
• rs72631820
• NM_001318252.2:c.130-12820A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001318252.2(CHLSN):​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: CHLSN NM_001318252.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 14 publications found

Genes affected

CHLSN (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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318252.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHLSN	NM_001318252.2	MANE Select	c.130-12820A>G		intron	N/A	NP_001305181.1
	MIR339	NR_029898.1		n.64A>G		non_coding_transcript_exon	Exon 1 of 1
	CHLSN	NM_001424325.1		c.130-12820A>G		intron	N/A	NP_001411254.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7orf50	ENST00000397098.8	TSL:1 MANE Select	c.130-12820A>G		intron	N/A	ENSP00000380286.3
	C7orf50	ENST00000357429.10	TSL:1	c.130-12820A>G		intron	N/A	ENSP00000350011.5
	MIR339	ENST00000362153.3	TSL:6	n.64A>G		non_coding_transcript_exon	Exon 1 of 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

GnomAD2 exomes AF: 0.00921 AC: 1464 AN: 158958 AF XY: 0.00995

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 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

African (AFR) AF: 0.0273 AC: 248 AN: 9068

American (AMR) AF: 0.00580 AC: 180 AN: 31016

Ashkenazi Jewish (ASJ) AF: 0.00937 AC: 103 AN: 10994

East Asian (EAS) AF: 0.00 AC: 0 AN: 9940

South Asian (SAS) AF: 0.0220 AC: 1332 AN: 60644

European-Finnish (FIN) AF: 0.00211 AC: 31 AN: 14704

Middle Eastern (MID) AF: 0.0261 AC: 70 AN: 2682

European-Non Finnish (NFE) AF: 0.00544 AC: 904 AN: 166110

Other (OTH) AF: 0.00803 AC: 117 AN: 14564

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

African (AFR) AF: 0.0275 AC: 1143 AN: 41576

American (AMR) AF: 0.0113 AC: 173 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4832

European-Finnish (FIN) AF: 0.00103 AC: 11 AN: 10628

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00595 AC: 405 AN: 68028

Other (OTH) AF: 0.0246 AC: 52 AN: 2114

Alfa AF: 0.0102 Hom.: 3

Bravo AF: 0.0140

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.74
PhyloP100		0.082
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs72631820; hg19: chr7-1062599;