rs10229820

Variant names:

• chr7-117548628-G-T
• rs10229820
• NM_000492.4:c.1210-13G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000492.4(CFTR):​c.1210-13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 1,542,054 control chromosomes in the GnomAD database, including 4,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (610 hom., cov: 30)
  • Exomes 𝑓: 0.078 (3879 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -0.455
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-117548628-G-T is Benign according to our data. Variant chr7-117548628-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 162962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	NM_000492.4	MANE Select	c.1210-13G>T		intron	N/A	NP_000483.3
	CFTR-AS1	NR_149084.1		n.222-6089C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.1210-13G>T		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000699602.1		c.1210-13G>T		intron	N/A	ENSP00000514471.1	A0A8V8TNH2
	CFTR	ENST00000889206.1		c.1210-13G>T		intron	N/A	ENSP00000559265.1

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 13483 AN: 142324 Hom.: 609 Cov.: 30

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0494

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.0831

Gnomad EAS AF: 0.00806

Gnomad SAS AF: 0.0540

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.0713 AC: 14618 AN: 205052 AF XY: 0.0718

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.0430

Gnomad ASJ exome AF: 0.0828

Gnomad EAS exome AF: 0.00522

Gnomad FIN exome AF: 0.0896

Gnomad NFE exome AF: 0.0856

Gnomad OTH exome AF: 0.0804

GnomAD4 exome AF: 0.0779 AC: 109019 AN: 1399628 Hom.: 3879 Cov.: 39 AF XY: 0.0778 AC XY: 54166 AN XY: 696312

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.122 AC: 3736 AN: 30598

American (AMR) AF: 0.0414 AC: 1743 AN: 42052

Ashkenazi Jewish (ASJ) AF: 0.0846 AC: 2042 AN: 24130

East Asian (EAS) AF: 0.00727 AC: 279 AN: 38362

South Asian (SAS) AF: 0.0551 AC: 4567 AN: 82876

European-Finnish (FIN) AF: 0.0918 AC: 4717 AN: 51356

Middle Eastern (MID) AF: 0.104 AC: 571 AN: 5516

European-Non Finnish (NFE) AF: 0.0814 AC: 86848 AN: 1067374

Other (OTH) AF: 0.0787 AC: 4516 AN: 57364

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0947 AC: 13494 AN: 142426 Hom.: 610 Cov.: 30 AF XY: 0.0935 AC XY: 6491 AN XY: 69442

African (AFR) AF: 0.131 AC: 4829 AN: 36904

American (AMR) AF: 0.0799 AC: 1149 AN: 14380

Ashkenazi Jewish (ASJ) AF: 0.0831 AC: 283 AN: 3406

East Asian (EAS) AF: 0.00769 AC: 39 AN: 5074

South Asian (SAS) AF: 0.0539 AC: 245 AN: 4548

European-Finnish (FIN) AF: 0.0838 AC: 808 AN: 9646

Middle Eastern (MID) AF: 0.115 AC: 32 AN: 278

European-Non Finnish (NFE) AF: 0.0896 AC: 5852 AN: 65336

Other (OTH) AF: 0.108 AC: 213 AN: 1964

Alfa AF: 0.0380 Hom.: 24

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	CFTR-related disorder (3)
-	-	2	not provided (2)
-	-	1	Cystic fibrosis (1)
-	-	1	Cystic fibrosis;C0238339:Hereditary pancreatitis;C0403814:Congenital bilateral aplasia of vas deferens from CFTR mutation;C2749757:Bronchiectasis with or without elevated sweat chloride 1 (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.031
DANN	Benign	0.23
PhyloP100		-0.46
Mutation Taster		=11/89	disease causing (long InDel)

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: rs10229820; hg19: chr7-117188682;