7-117427768-T-G

Variant names:

• chr7-117427768-T-G
• rs7808424
• ENST00000673785.1:c.-490-37979T>G

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The ENST00000673785.1(CFTR):c.-490-37979T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000673785.1 is not a MANE Select or MANE Plus Clinical transcript for CFTR; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.112 (AC=17,068) in the gnomAD database across 152,248 control chromosomes, including 1,534 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.433. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1534 hom., cov: 32)
• Consequence: CFTR ENST00000673785.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 19 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 Gene-Disease associations (from GenCC):

• congenital bilateral aplasia of vas deferens from CFTR mutation

  Inheritance: AR Classification: DEFINITIVE Submitted by: Natera
• cystic fibrosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Myriad Women's Health, ClinGen, Natera, Orphanet
• congenital bilateral absence of vas deferens

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary chronic pancreatitis

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ASZ1 (HGNC:1350): (ankyrin repeat, SAM and basic leucine zipper domain containing 1) Predicted to be involved in male meiotic nuclear division; spermatogenesis; and transposable element silencing. Predicted to be located in cytoplasm. Predicted to be active in pi-body. [provided by Alliance of Genome Resources, Jul 2025]

ASZ1 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.4331 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000673785.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CFTR ENST00000673785.1		c.-490-37979T>G	intron	Intron 2 of 12	Prot: ENSP00000501235.1 UniProt:
	ASZ1 ENST00000428663.1	TSL:5	c.-55+302A>C	intron	Intron 1 of 2	Prot: ENSP00000402919.1 UniProt:

CFTR ENST00000673785.1

HGVSc / HGVSpc.-490-37979T>G

Exon rankIntron 2 of 12

intron

Prot: ENSP00000501235.1UniProt: A0A669KBE8

ASZ1 ENST00000428663.1

TSL:5

HGVSc / HGVSpc.-55+302A>C

Exon rankIntron 1 of 2

intron

Prot: ENSP00000402919.1UniProt: C9JP59

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.112	AC:17047	Hom:1527	AN:152130	Cov:32
GnomAD4 genome	AF: 0.112	AC:17068	Hom:1534	AN:152248	Cov:32
TOPMed (Bravo)	AF: 0.119	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.103	AC:52790	Hom:4324	AN:512918	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.104	AC:244	Hom:17	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.482	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.0333	AC:10	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.372	AC:1295	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.482	AC:3487	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.0682	AC:12	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.418	AC:51356	Hom:10804	AN:122810	Cov:
Turkish Variome	AF: 0.0737	AC:114	Hom:2	AN:1546	Cov:
UK10K	AF: 0.0841	AC:636	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.455	AC:4076	Hom:947	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	10
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.75
GPN-Star LLR	N/A	0.73
GPN-Star score	N/A	-0.73
PhyloP100	Benign	-0.037
PromoterAI	N/A	0.018	Neutral

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.010

Showing 1 of 1 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs7808424;

hg19: chr7-117067822;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar