rs7041716

Variant names:

• chr9-109046157-C-A
• rs7041716
• NM_032012.4:c.2123+4126G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-109046157-C-A
• chr9-109046157-C-G

Variant summary

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

The NM_032012.4(TMEM245):​c.2123+4126G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 511,074 control chromosomes in the GnomAD database, including 4,150 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 0.090 (731 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3419 hom.)
• Consequence: TMEM245 NM_032012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 8 publications found

Genes affected

TMEM245 (HGNC:1363): (transmembrane protein 245) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MIR32 (HGNC:31631): (microRNA 32) 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=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032012.4. 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
	TMEM245	NM_032012.4	MANE Select	c.2123+4126G>T		intron	N/A	NP_114401.2	Q9H330-2
	TMEM245	NM_001438164.1		c.2120+4126G>T		intron	N/A	NP_001425093.1
	TMEM245	NM_001438005.1		c.2099+4126G>T		intron	N/A	NP_001424934.1	H7C0G1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM245	ENST00000374586.8	TSL:1 MANE Select	c.2123+4126G>T		intron	N/A	ENSP00000363714.3	Q9H330-2
	TMEM245	ENST00000894214.1		c.2120+4126G>T		intron	N/A	ENSP00000564273.1
	TMEM245	ENST00000952009.1		c.2117+4126G>T		intron	N/A	ENSP00000622068.1

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13685 AN: 151940 Hom.: 729 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0901

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0856

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0875

GnomAD4 exome AF: 0.126 AC: 45248 AN: 359016 Hom.: 3419 AF XY: 0.135 AC XY: 27549 AN XY: 203510

African (AFR) AF: 0.0375 AC: 386 AN: 10304

American (AMR) AF: 0.114 AC: 4013 AN: 35194

Ashkenazi Jewish (ASJ) AF: 0.0985 AC: 1068 AN: 10844

East Asian (EAS) AF: 0.141 AC: 1794 AN: 12718

South Asian (SAS) AF: 0.228 AC: 14562 AN: 63986

European-Finnish (FIN) AF: 0.0916 AC: 2744 AN: 29960

Middle Eastern (MID) AF: 0.0933 AC: 260 AN: 2788

European-Non Finnish (NFE) AF: 0.105 AC: 18632 AN: 177492

Other (OTH) AF: 0.114 AC: 1789 AN: 15730

GnomAD4 genome AF: 0.0901 AC: 13698 AN: 152058 Hom.: 731 Cov.: 32 AF XY: 0.0923 AC XY: 6860 AN XY: 74320

African (AFR) AF: 0.0390 AC: 1619 AN: 41488

American (AMR) AF: 0.0906 AC: 1384 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 340 AN: 3472

East Asian (EAS) AF: 0.137 AC: 708 AN: 5172

South Asian (SAS) AF: 0.241 AC: 1159 AN: 4818

European-Finnish (FIN) AF: 0.0856 AC: 901 AN: 10528

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7217 AN: 67986

Other (OTH) AF: 0.0885 AC: 187 AN: 2114

Alfa AF: 0.0472 Hom.: 51

Bravo AF: 0.0851

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.3
DANN	Benign	0.82
PhyloP100		-0.33
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: rs7041716; hg19: chr9-111808437; COSMIC: COSV63026314; COSMIC: COSV63026314;