rs10487372

Variant names:

• chr7-117560845-C-T
• rs10487372
• NM_000492.4:c.1584+1190C>T

Variant summary

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

The NM_000492.4(CFTR):​c.1584+1190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 151,860 control chromosomes in the GnomAD database, including 1,275 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 0.12 (1275 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 11 publications found

Genes affected

CFTR (HGNC:1884): (CF transmembrane conductance regulator) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]

CFTR-AS1 (HGNC:40144): (CFTR antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000492.4. 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
	CFTR	NM_000492.4	MANE Select	c.1584+1190C>T		intron	N/A	NP_000483.3
	CFTR-AS1	NR_149084.1		n.162-53G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.1584+1190C>T		intron	N/A	ENSP00000003084.6
	CFTR	ENST00000699602.1		c.1584+1190C>T		intron	N/A	ENSP00000514471.1
	CFTR	ENST00000426809.5	TSL:5	c.1494+1190C>T		intron	N/A	ENSP00000389119.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18784 AN: 151740 Hom.: 1269 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.0827

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.124 AC: 18816 AN: 151860 Hom.: 1275 Cov.: 32 AF XY: 0.127 AC XY: 9390 AN XY: 74200

African (AFR) AF: 0.147 AC: 6106 AN: 41440

American (AMR) AF: 0.0917 AC: 1400 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 362 AN: 3460

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5178

South Asian (SAS) AF: 0.0826 AC: 398 AN: 4818

European-Finnish (FIN) AF: 0.205 AC: 2152 AN: 10518

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7964 AN: 67858

Other (OTH) AF: 0.129 AC: 271 AN: 2108

Alfa AF: 0.113 Hom.: 1639

Bravo AF: 0.116

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.38
PhyloP100		-0.010
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: rs10487372; hg19: chr7-117200899;