7-135159223-A-G

Position:

• chr7-135159223-A-G

Variant summary

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

The NM_018295.5(TMEM140):​c.-24-5195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,094 control chromosomes in the GnomAD database, including 17,737 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 0.48 (17737 hom., cov: 33)
• Consequence: TMEM140 NM_018295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM140	NM_018295.5	c.-24-5195A>G		intron_variant		ENST00000275767.3	NP_060765.4
CYREN	NM_001305630.2	c.174+9526T>C		intron_variant			NP_001292559.1
CYREN	XM_017012595.2	c.*40+8509T>C		intron_variant			XP_016868084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM140	ENST00000275767.3	c.-24-5195A>G		intron_variant		1	NM_018295.5	ENSP00000275767.2
CYREN	ENST00000459937.5	n.356+9526T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72692 AN: 151976 Hom.: 17715 Cov.: 33

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.478 AC: 72771 AN: 152094 Hom.: 17737 Cov.: 33 AF XY: 0.478 AC XY: 35568 AN XY: 74348

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.475

Alfa AF: 0.485 Hom.: 2982

Bravo AF: 0.473

Asia WGS AF: 0.481 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.69

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: rs1035695; hg19: chr7-134843975;