rs3735001

Positions:

• chr7-135148462-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018295.5(TMEM140):​c.-25+192C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,190 control chromosomes in the GnomAD database, including 5,750 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 0.26 (5750 hom., cov: 33)
• Consequence: TMEM140 NM_018295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855

Genes affected

TMEM140 (HGNC:21870): (transmembrane protein 140) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CYREN (HGNC:):

CYREN (HGNC:22432): (cell cycle regulator of NHEJ) Involved in double-strand break repair via nonhomologous end joining and negative regulation of double-strand break repair via nonhomologous end joining. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM140	NM_018295.5	c.-25+192C>A		intron_variant		ENST00000275767.3	NP_060765.4
CYREN	NM_001305630.2	c.174+20287G>T		intron_variant			NP_001292559.1
CYREN	XM_017012595.2	c.*40+19270G>T		intron_variant			XP_016868084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM140	ENST00000275767.3	c.-25+192C>A		intron_variant		1	NM_018295.5	ENSP00000275767.2
CYREN	ENST00000459937.5	n.356+20287G>T		intron_variant		1
TMEM140	ENST00000466307.1	n.76+192C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39449 AN: 152074 Hom.: 5751 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.259 AC: 39457 AN: 152190 Hom.: 5750 Cov.: 33 AF XY: 0.262 AC XY: 19486 AN XY: 74400

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.277

Alfa AF: 0.274 Hom.: 757

Bravo AF: 0.263

Asia WGS AF: 0.350 AC: 1214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.7
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3735001; hg19: chr7-134833214;